Impaired nonhomologous end-joining in mismatch repair-deficient colon carcinomas View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-07-18

AUTHORS

Kwi H Koh, Hyun J Kang, Long S Li, Nam-Gyun Kim, Kwon T You, Eungi Yang, Hyunki Kim, Hee J Kim, Chae-Ok Yun, Kyung-Sup Kim, Hoguen Kim

ABSTRACT

Frameshift mutations of coding mononucleotide repeat of the hRAD50 gene and formation of the mutant hMRE11 splicing variant are frequent events in tumors with mismatch repair (MMR) deficiency. Both the hRAD50 and hMRE11 proteins form a heterotrimer with the NBS1, and this heterotrimer is involved in the double strand DNA break repair by homologous recombination and nonhomologous end-joining (NHEJ). In order to clarify the role of hRAD50 and hMRE11 gene alterations in MMR-deficient tumors, we analyzed the expression of the hRAD50 and hMRE11 proteins and we evaluated NHEJ in the seven MMR-deficient and five MMR-proficient colon cancer cell lines. Frameshift mutations of the hRAD50 gene were found in five of seven MMR-deficient cell lines, and this was directly related to the decreased expression of hRAD50 mRNA and protein. The mutant hMRE11 splicing variant was found in all of the seven MMR-deficient cell lines, and this was related to the decreased hMRE11 expression in four of the seven MMR-deficient cell lines. MMR-deficient cell lines with decreased hRAD50 and hMRE11 expressions were more sensitive to γ-irradiation, and these cell lines showed an impaired NHEJ. The impairment of NHEJ was induced after knockdown of hRAD50 and hMRE11 through small interference RNA. Our findings suggest that mutations of hRAD50 and hMRE11 genes in MMR-deficient tumors are related to the defects in NHEJ, and this may result in chromosomal changes during the progression of tumor. More... »

PAGES

1130-1138

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/labinvest.3700315

DOI

http://dx.doi.org/10.1038/labinvest.3700315

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1045992115

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16025146


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Acid Anhydride Hydrolases", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Base Pair Mismatch", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Base Sequence", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Line, Tumor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Colonic Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA Primers", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA Repair", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA Repair Enzymes", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA-Binding Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Immunoprecipitation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "RNA Splicing", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "RNA, Small Interfering", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Recombination, Genetic", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.15444.30", 
          "name": [
            "Department of Pathology, Yonsei University College of Medicine, Seoul, Korea", 
            "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Koh", 
        "givenName": "Kwi H", 
        "id": "sg:person.0732662117.21", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0732662117.21"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.15444.30", 
          "name": [
            "Department of Pathology, Yonsei University College of Medicine, Seoul, Korea", 
            "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kang", 
        "givenName": "Hyun J", 
        "id": "sg:person.01030460171.44", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01030460171.44"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.15444.30", 
          "name": [
            "Department of Pathology, Yonsei University College of Medicine, Seoul, Korea", 
            "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Li", 
        "givenName": "Long S", 
        "id": "sg:person.0711246544.06", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0711246544.06"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.15444.30", 
          "name": [
            "Department of Pathology, Yonsei University College of Medicine, Seoul, Korea", 
            "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kim", 
        "givenName": "Nam-Gyun", 
        "id": "sg:person.01233362377.86", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01233362377.86"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.15444.30", 
          "name": [
            "Department of Pathology, Yonsei University College of Medicine, Seoul, Korea", 
            "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "You", 
        "givenName": "Kwon T", 
        "id": "sg:person.01144706571.21", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01144706571.21"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.15444.30", 
          "name": [
            "Department of Pathology, Yonsei University College of Medicine, Seoul, Korea", 
            "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yang", 
        "givenName": "Eungi", 
        "id": "sg:person.01076573371.16", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01076573371.16"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.15444.30", 
          "name": [
            "Department of Pathology, Yonsei University College of Medicine, Seoul, Korea", 
            "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kim", 
        "givenName": "Hyunki", 
        "id": "sg:person.01061166771.52", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01061166771.52"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Pathology, Yonsei University College of Medicine, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.15444.30", 
          "name": [
            "Department of Pathology, Yonsei University College of Medicine, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kim", 
        "givenName": "Hee J", 
        "id": "sg:person.0672320077.11", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0672320077.11"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.15444.30", 
          "name": [
            "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea", 
            "Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yun", 
        "givenName": "Chae-Ok", 
        "id": "sg:person.01257734374.56", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01257734374.56"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.15444.30", 
          "name": [
            "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea", 
            "Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kim", 
        "givenName": "Kyung-Sup", 
        "id": "sg:person.01032405333.42", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01032405333.42"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.15444.30", 
          "name": [
            "Department of Pathology, Yonsei University College of Medicine, Seoul, Korea", 
            "Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kim", 
        "givenName": "Hoguen", 
        "id": "sg:person.01003376625.30", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01003376625.30"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/sj.onc.1205703", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031543682", 
          "https://doi.org/10.1038/sj.onc.1205703"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/25292", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033871070", 
          "https://doi.org/10.1038/25292"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1206580", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044543096", 
          "https://doi.org/10.1038/sj.onc.1206580"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/12687", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005809393", 
          "https://doi.org/10.1038/12687"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/bcr362", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009419544", 
          "https://doi.org/10.1186/bcr362"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35101065", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013162307", 
          "https://doi.org/10.1038/35101065"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35056049", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028620907", 
          "https://doi.org/10.1038/35056049"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/363558a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043263395", 
          "https://doi.org/10.1038/363558a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng1215", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015362478", 
          "https://doi.org/10.1038/ng1215"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2005-07-18", 
    "datePublishedReg": "2005-07-18", 
    "description": "Frameshift mutations of coding mononucleotide repeat of the hRAD50 gene and formation of the mutant hMRE11 splicing variant are frequent events in tumors with mismatch repair (MMR) deficiency. Both the hRAD50 and hMRE11 proteins form a heterotrimer with the NBS1, and this heterotrimer is involved in the double strand DNA break repair by homologous recombination and nonhomologous end-joining (NHEJ). In order to clarify the role of hRAD50 and hMRE11 gene alterations in MMR-deficient tumors, we analyzed the expression of the hRAD50 and hMRE11 proteins and we evaluated NHEJ in the seven MMR-deficient and five MMR-proficient colon cancer cell lines. Frameshift mutations of the hRAD50 gene were found in five of seven MMR-deficient cell lines, and this was directly related to the decreased expression of hRAD50 mRNA and protein. The mutant hMRE11 splicing variant was found in all of the seven MMR-deficient cell lines, and this was related to the decreased hMRE11 expression in four of the seven MMR-deficient cell lines. MMR-deficient cell lines with decreased hRAD50 and hMRE11 expressions were more sensitive to \u03b3-irradiation, and these cell lines showed an impaired NHEJ. The impairment of NHEJ was induced after knockdown of hRAD50 and hMRE11 through small interference RNA. Our findings suggest that mutations of hRAD50 and hMRE11 genes in MMR-deficient tumors are related to the defects in NHEJ, and this may result in chromosomal changes during the progression of tumor.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/labinvest.3700315", 
    "inLanguage": "en", 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1017964", 
        "issn": [
          "0023-6837", 
          "1530-0307"
        ], 
        "name": "Laboratory Investigation", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "9", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "85"
      }
    ], 
    "keywords": [
      "MMR-deficient cell lines", 
      "splicing variants", 
      "strand DNA break repair", 
      "cell lines", 
      "double-strand DNA break repair", 
      "DNA break repair", 
      "frameshift mutation", 
      "colon cancer cell lines", 
      "small interference RNA", 
      "impaired NHEJ", 
      "break repair", 
      "homologous recombination", 
      "NHEJ", 
      "progression of tumors", 
      "interference RNA", 
      "hRAD50", 
      "cancer cell lines", 
      "mononucleotide repeats", 
      "genes", 
      "chromosomal changes", 
      "protein", 
      "heterotrimer", 
      "mutations", 
      "decreased expression", 
      "MMR-deficient tumors", 
      "repair deficiency", 
      "gene alterations", 
      "expression", 
      "frequent event", 
      "NBS1", 
      "hMRE11", 
      "mismatch repair deficiency", 
      "repeats", 
      "knockdown", 
      "RNA", 
      "variants", 
      "lines", 
      "mRNA", 
      "colon carcinoma", 
      "recombination", 
      "tumors", 
      "alterations", 
      "repair", 
      "role", 
      "progression", 
      "deficiency", 
      "defects", 
      "formation", 
      "carcinoma", 
      "impairment", 
      "events", 
      "changes", 
      "findings", 
      "irradiation", 
      "order", 
      "hRAD50 gene", 
      "mutant hMRE11 splicing variant", 
      "hMRE11 splicing variant", 
      "hMRE11 proteins", 
      "role of hRAD50", 
      "hMRE11 gene alterations", 
      "MMR-proficient colon cancer cell lines", 
      "hRAD50 mRNA", 
      "decreased hMRE11 expression", 
      "hMRE11 expression", 
      "impairment of NHEJ", 
      "knockdown of hRAD50", 
      "mutations of hRAD50", 
      "hMRE11 genes", 
      "mismatch repair-deficient colon carcinomas", 
      "repair-deficient colon carcinomas"
    ], 
    "name": "Impaired nonhomologous end-joining in mismatch repair-deficient colon carcinomas", 
    "pagination": "1130-1138", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1045992115"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/labinvest.3700315"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "16025146"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/labinvest.3700315", 
      "https://app.dimensions.ai/details/publication/pub.1045992115"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-01-01T18:15", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220101/entities/gbq_results/article/article_411.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/labinvest.3700315"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/labinvest.3700315'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/labinvest.3700315'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/labinvest.3700315'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/labinvest.3700315'


 

This table displays all metadata directly associated to this object as RDF triples.

301 TRIPLES      22 PREDICATES      120 URIs      103 LITERALS      21 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/labinvest.3700315 schema:about N14df0a443e634e7bb656f35ca518a670
2 N1880ab21bca24a0ea499815631559e3a
3 N18b67ad1aa70430bb1145f2614ca25a6
4 N18bcd59ce99f48dbbec5242d95d9a41c
5 N3d238ca2db264dd1988452eadf5af0a4
6 N4f4bc11e54b34c7cb07841c118b36fd3
7 N52cc836aeca64be884a024a545dabd18
8 N59c4ea11de2746c8b51609056e6f7f36
9 N5e941547dc044682b5ef4bdc73722e02
10 N5fd0f33d85d942fb9752c2f7e2924bea
11 N7a91918e465a4c059ebe37d897f46062
12 N8b434ab7f39842ad9cd2ee40b04770b2
13 N9a811ae8764b4fcbbcbbb0668c067241
14 Nadfaa4a0b12446bdacfc05c53d15cb45
15 anzsrc-for:11
16 anzsrc-for:1112
17 schema:author N474884dbb37a4d1fb2c36e16c610630b
18 schema:citation sg:pub.10.1038/12687
19 sg:pub.10.1038/25292
20 sg:pub.10.1038/35056049
21 sg:pub.10.1038/35101065
22 sg:pub.10.1038/363558a0
23 sg:pub.10.1038/ng1215
24 sg:pub.10.1038/sj.onc.1205703
25 sg:pub.10.1038/sj.onc.1206580
26 sg:pub.10.1186/bcr362
27 schema:datePublished 2005-07-18
28 schema:datePublishedReg 2005-07-18
29 schema:description Frameshift mutations of coding mononucleotide repeat of the hRAD50 gene and formation of the mutant hMRE11 splicing variant are frequent events in tumors with mismatch repair (MMR) deficiency. Both the hRAD50 and hMRE11 proteins form a heterotrimer with the NBS1, and this heterotrimer is involved in the double strand DNA break repair by homologous recombination and nonhomologous end-joining (NHEJ). In order to clarify the role of hRAD50 and hMRE11 gene alterations in MMR-deficient tumors, we analyzed the expression of the hRAD50 and hMRE11 proteins and we evaluated NHEJ in the seven MMR-deficient and five MMR-proficient colon cancer cell lines. Frameshift mutations of the hRAD50 gene were found in five of seven MMR-deficient cell lines, and this was directly related to the decreased expression of hRAD50 mRNA and protein. The mutant hMRE11 splicing variant was found in all of the seven MMR-deficient cell lines, and this was related to the decreased hMRE11 expression in four of the seven MMR-deficient cell lines. MMR-deficient cell lines with decreased hRAD50 and hMRE11 expressions were more sensitive to γ-irradiation, and these cell lines showed an impaired NHEJ. The impairment of NHEJ was induced after knockdown of hRAD50 and hMRE11 through small interference RNA. Our findings suggest that mutations of hRAD50 and hMRE11 genes in MMR-deficient tumors are related to the defects in NHEJ, and this may result in chromosomal changes during the progression of tumor.
30 schema:genre article
31 schema:inLanguage en
32 schema:isAccessibleForFree true
33 schema:isPartOf N097796a738b64953a5e5f73d5522e1ff
34 N3f0c036057a246d8bab14fa783c3726c
35 sg:journal.1017964
36 schema:keywords DNA break repair
37 MMR-deficient cell lines
38 MMR-deficient tumors
39 MMR-proficient colon cancer cell lines
40 NBS1
41 NHEJ
42 RNA
43 alterations
44 break repair
45 cancer cell lines
46 carcinoma
47 cell lines
48 changes
49 chromosomal changes
50 colon cancer cell lines
51 colon carcinoma
52 decreased expression
53 decreased hMRE11 expression
54 defects
55 deficiency
56 double-strand DNA break repair
57 events
58 expression
59 findings
60 formation
61 frameshift mutation
62 frequent event
63 gene alterations
64 genes
65 hMRE11
66 hMRE11 expression
67 hMRE11 gene alterations
68 hMRE11 genes
69 hMRE11 proteins
70 hMRE11 splicing variant
71 hRAD50
72 hRAD50 gene
73 hRAD50 mRNA
74 heterotrimer
75 homologous recombination
76 impaired NHEJ
77 impairment
78 impairment of NHEJ
79 interference RNA
80 irradiation
81 knockdown
82 knockdown of hRAD50
83 lines
84 mRNA
85 mismatch repair deficiency
86 mismatch repair-deficient colon carcinomas
87 mononucleotide repeats
88 mutant hMRE11 splicing variant
89 mutations
90 mutations of hRAD50
91 order
92 progression
93 progression of tumors
94 protein
95 recombination
96 repair
97 repair deficiency
98 repair-deficient colon carcinomas
99 repeats
100 role
101 role of hRAD50
102 small interference RNA
103 splicing variants
104 strand DNA break repair
105 tumors
106 variants
107 schema:name Impaired nonhomologous end-joining in mismatch repair-deficient colon carcinomas
108 schema:pagination 1130-1138
109 schema:productId N9c7d2361f63d44b18751c0b9716d69a6
110 Nabeca716ba454bcbbbade17819cbb1ed
111 Nf15bdf45b23e4ec489c319784118ab22
112 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045992115
113 https://doi.org/10.1038/labinvest.3700315
114 schema:sdDatePublished 2022-01-01T18:15
115 schema:sdLicense https://scigraph.springernature.com/explorer/license/
116 schema:sdPublisher N11169e0385ec4d929c6e58f5324a6418
117 schema:url https://doi.org/10.1038/labinvest.3700315
118 sgo:license sg:explorer/license/
119 sgo:sdDataset articles
120 rdf:type schema:ScholarlyArticle
121 N097796a738b64953a5e5f73d5522e1ff schema:issueNumber 9
122 rdf:type schema:PublicationIssue
123 N11169e0385ec4d929c6e58f5324a6418 schema:name Springer Nature - SN SciGraph project
124 rdf:type schema:Organization
125 N14df0a443e634e7bb656f35ca518a670 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
126 schema:name DNA-Binding Proteins
127 rdf:type schema:DefinedTerm
128 N1791fed2d0294936b085c6b72d62e831 rdf:first sg:person.01061166771.52
129 rdf:rest Na199948a67b0496aa84568ab42c28c40
130 N1880ab21bca24a0ea499815631559e3a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
131 schema:name Colonic Neoplasms
132 rdf:type schema:DefinedTerm
133 N18b67ad1aa70430bb1145f2614ca25a6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
134 schema:name Acid Anhydride Hydrolases
135 rdf:type schema:DefinedTerm
136 N18bcd59ce99f48dbbec5242d95d9a41c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
137 schema:name DNA Repair
138 rdf:type schema:DefinedTerm
139 N3d238ca2db264dd1988452eadf5af0a4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
140 schema:name DNA Repair Enzymes
141 rdf:type schema:DefinedTerm
142 N3f0c036057a246d8bab14fa783c3726c schema:volumeNumber 85
143 rdf:type schema:PublicationVolume
144 N474884dbb37a4d1fb2c36e16c610630b rdf:first sg:person.0732662117.21
145 rdf:rest N8c993c3b35094e9d8989622c262286fe
146 N4890d31983b449e6af850fb1aa28862e rdf:first sg:person.01032405333.42
147 rdf:rest Ne1161d3276114b828a3d9ca70e148823
148 N4f4bc11e54b34c7cb07841c118b36fd3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
149 schema:name RNA, Small Interfering
150 rdf:type schema:DefinedTerm
151 N52cc836aeca64be884a024a545dabd18 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
152 schema:name Base Pair Mismatch
153 rdf:type schema:DefinedTerm
154 N59c4ea11de2746c8b51609056e6f7f36 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
155 schema:name Recombination, Genetic
156 rdf:type schema:DefinedTerm
157 N5e941547dc044682b5ef4bdc73722e02 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
158 schema:name Immunoprecipitation
159 rdf:type schema:DefinedTerm
160 N5fd0f33d85d942fb9752c2f7e2924bea schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
161 schema:name DNA Primers
162 rdf:type schema:DefinedTerm
163 N60adf681f60d47bea168221b35d5ebd1 rdf:first sg:person.01076573371.16
164 rdf:rest N1791fed2d0294936b085c6b72d62e831
165 N7a91918e465a4c059ebe37d897f46062 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
166 schema:name RNA Splicing
167 rdf:type schema:DefinedTerm
168 N8b434ab7f39842ad9cd2ee40b04770b2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
169 schema:name Humans
170 rdf:type schema:DefinedTerm
171 N8c993c3b35094e9d8989622c262286fe rdf:first sg:person.01030460171.44
172 rdf:rest Nd34510d4449e426b94e16a90e4b197a3
173 N9a811ae8764b4fcbbcbbb0668c067241 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
174 schema:name Cell Line, Tumor
175 rdf:type schema:DefinedTerm
176 N9c7d2361f63d44b18751c0b9716d69a6 schema:name doi
177 schema:value 10.1038/labinvest.3700315
178 rdf:type schema:PropertyValue
179 N9cef4d7b609049d782a5aa23abd031a3 rdf:first sg:person.01257734374.56
180 rdf:rest N4890d31983b449e6af850fb1aa28862e
181 Na199948a67b0496aa84568ab42c28c40 rdf:first sg:person.0672320077.11
182 rdf:rest N9cef4d7b609049d782a5aa23abd031a3
183 Nabeca716ba454bcbbbade17819cbb1ed schema:name pubmed_id
184 schema:value 16025146
185 rdf:type schema:PropertyValue
186 Nadfaa4a0b12446bdacfc05c53d15cb45 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
187 schema:name Base Sequence
188 rdf:type schema:DefinedTerm
189 Nbd50d6e6a1fc433795e04337f325c08f rdf:first sg:person.01144706571.21
190 rdf:rest N60adf681f60d47bea168221b35d5ebd1
191 Nc286b6ce3906474d9a29333e811f61f6 rdf:first sg:person.01233362377.86
192 rdf:rest Nbd50d6e6a1fc433795e04337f325c08f
193 Nd34510d4449e426b94e16a90e4b197a3 rdf:first sg:person.0711246544.06
194 rdf:rest Nc286b6ce3906474d9a29333e811f61f6
195 Ne1161d3276114b828a3d9ca70e148823 rdf:first sg:person.01003376625.30
196 rdf:rest rdf:nil
197 Nf15bdf45b23e4ec489c319784118ab22 schema:name dimensions_id
198 schema:value pub.1045992115
199 rdf:type schema:PropertyValue
200 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
201 schema:name Medical and Health Sciences
202 rdf:type schema:DefinedTerm
203 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
204 schema:name Oncology and Carcinogenesis
205 rdf:type schema:DefinedTerm
206 sg:journal.1017964 schema:issn 0023-6837
207 1530-0307
208 schema:name Laboratory Investigation
209 schema:publisher Springer Nature
210 rdf:type schema:Periodical
211 sg:person.01003376625.30 schema:affiliation grid-institutes:grid.15444.30
212 schema:familyName Kim
213 schema:givenName Hoguen
214 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01003376625.30
215 rdf:type schema:Person
216 sg:person.01030460171.44 schema:affiliation grid-institutes:grid.15444.30
217 schema:familyName Kang
218 schema:givenName Hyun J
219 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01030460171.44
220 rdf:type schema:Person
221 sg:person.01032405333.42 schema:affiliation grid-institutes:grid.15444.30
222 schema:familyName Kim
223 schema:givenName Kyung-Sup
224 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01032405333.42
225 rdf:type schema:Person
226 sg:person.01061166771.52 schema:affiliation grid-institutes:grid.15444.30
227 schema:familyName Kim
228 schema:givenName Hyunki
229 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01061166771.52
230 rdf:type schema:Person
231 sg:person.01076573371.16 schema:affiliation grid-institutes:grid.15444.30
232 schema:familyName Yang
233 schema:givenName Eungi
234 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01076573371.16
235 rdf:type schema:Person
236 sg:person.01144706571.21 schema:affiliation grid-institutes:grid.15444.30
237 schema:familyName You
238 schema:givenName Kwon T
239 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01144706571.21
240 rdf:type schema:Person
241 sg:person.01233362377.86 schema:affiliation grid-institutes:grid.15444.30
242 schema:familyName Kim
243 schema:givenName Nam-Gyun
244 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01233362377.86
245 rdf:type schema:Person
246 sg:person.01257734374.56 schema:affiliation grid-institutes:grid.15444.30
247 schema:familyName Yun
248 schema:givenName Chae-Ok
249 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01257734374.56
250 rdf:type schema:Person
251 sg:person.0672320077.11 schema:affiliation grid-institutes:grid.15444.30
252 schema:familyName Kim
253 schema:givenName Hee J
254 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0672320077.11
255 rdf:type schema:Person
256 sg:person.0711246544.06 schema:affiliation grid-institutes:grid.15444.30
257 schema:familyName Li
258 schema:givenName Long S
259 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0711246544.06
260 rdf:type schema:Person
261 sg:person.0732662117.21 schema:affiliation grid-institutes:grid.15444.30
262 schema:familyName Koh
263 schema:givenName Kwi H
264 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0732662117.21
265 rdf:type schema:Person
266 sg:pub.10.1038/12687 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005809393
267 https://doi.org/10.1038/12687
268 rdf:type schema:CreativeWork
269 sg:pub.10.1038/25292 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033871070
270 https://doi.org/10.1038/25292
271 rdf:type schema:CreativeWork
272 sg:pub.10.1038/35056049 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028620907
273 https://doi.org/10.1038/35056049
274 rdf:type schema:CreativeWork
275 sg:pub.10.1038/35101065 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013162307
276 https://doi.org/10.1038/35101065
277 rdf:type schema:CreativeWork
278 sg:pub.10.1038/363558a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043263395
279 https://doi.org/10.1038/363558a0
280 rdf:type schema:CreativeWork
281 sg:pub.10.1038/ng1215 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015362478
282 https://doi.org/10.1038/ng1215
283 rdf:type schema:CreativeWork
284 sg:pub.10.1038/sj.onc.1205703 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031543682
285 https://doi.org/10.1038/sj.onc.1205703
286 rdf:type schema:CreativeWork
287 sg:pub.10.1038/sj.onc.1206580 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044543096
288 https://doi.org/10.1038/sj.onc.1206580
289 rdf:type schema:CreativeWork
290 sg:pub.10.1186/bcr362 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009419544
291 https://doi.org/10.1186/bcr362
292 rdf:type schema:CreativeWork
293 grid-institutes:grid.15444.30 schema:alternateName Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea
294 Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea
295 Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
296 Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
297 schema:name Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul, Korea
298 Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea
299 Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
300 Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
301 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...