Guanine- 5-carboxylcytosine base pairs mimic mismatches during DNA replication View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-06-09

AUTHORS

Toshihiro Shibutani, Shinsuke Ito, Mariko Toda, Rie Kanao, Leonard B. Collins, Marika Shibata, Miho Urabe, Haruhiko Koseki, Yuji Masuda, James A. Swenberg, Chikahide Masutani, Fumio Hanaoka, Shigenori Iwai, Isao Kuraoka

ABSTRACT

The genetic information encoded in genomes must be faithfully replicated and transmitted to daughter cells. The recent discovery of consecutive DNA conversions by TET family proteins of 5-methylcytosine into 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine (5caC) suggests these modified cytosines act as DNA lesions, which could threaten genome integrity. Here, we have shown that although 5caC pairs with guanine during DNA replication in vitro, G·5caC pairs stimulated DNA polymerase exonuclease activity and were recognized by the mismatch repair (MMR) proteins. Knockdown of thymine DNA glycosylase increased 5caC in genome, affected cell proliferation via MMR, indicating MMR is a novel reader for 5caC. These results suggest the epigenetic modification products of 5caC behave as DNA lesions. More... »

PAGES

5220

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep05220

DOI

http://dx.doi.org/10.1038/srep05220

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017233606

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24910358


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29 schema:description The genetic information encoded in genomes must be faithfully replicated and transmitted to daughter cells. The recent discovery of consecutive DNA conversions by TET family proteins of 5-methylcytosine into 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine (5caC) suggests these modified cytosines act as DNA lesions, which could threaten genome integrity. Here, we have shown that although 5caC pairs with guanine during DNA replication in vitro, G·5caC pairs stimulated DNA polymerase exonuclease activity and were recognized by the mismatch repair (MMR) proteins. Knockdown of thymine DNA glycosylase increased 5caC in genome, affected cell proliferation via MMR, indicating MMR is a novel reader for 5caC. These results suggest the epigenetic modification products of 5caC behave as DNA lesions.
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37 DNA glycosylase
38 DNA lesions
39 DNA polymerase exonuclease activity
40 DNA replication
41 Guanine- 5-carboxylcytosine base pairs mimic mismatches
42 MMR
43 TET family proteins
44 activity
45 acts
46 affected cell proliferation
47 base pairs mimic mismatches
48 behave
49 cell proliferation
50 cells
51 consecutive DNA conversions
52 conversion
53 cytosines act
54 daughter cells
55 discovery
56 epigenetic modification products
57 exonuclease activity
58 family proteins
59 genetic information
60 genome
61 genome integrity
62 glycosylase
63 guanine
64 information
65 integrity
66 knockdown
67 lesions
68 mimic mismatches
69 mismatch
70 mismatch repair proteins
71 modification products
72 novel readers
73 pairs
74 pairs mimic mismatches
75 polymerase exonuclease activity
76 products
77 proliferation
78 protein
79 readers
80 recent discovery
81 repair proteins
82 replication
83 results
84 thymine DNA glycosylase
85 vitro
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