Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2000-05

AUTHORS

Song Zhao, Yi-Chinn Weng, Shyng-Shiou F. Yuan, Yi-Tzu Lin, Hao-Chi Hsu, Suh-Chin J. Lin, Elvira Gerbino, Mei-hua Song, Malgorzata Z. Zdzienicka, Richard A. Gatti, Jerry W. Shay, Yael Ziv, Yosef Shiloh, Eva Y.-H. P. Lee

ABSTRACT

Ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are recessive genetic disorders with susceptibility to cancer and similar cellular phenotypes. The protein product of the gene responsible for A-T, designated ATM, is a member of a family of kinases characterized by a carboxy-terminal phosphatidylinositol 3-kinase-like domain. The NBS1 protein is specifically mutated in patients with Nijmegen breakage syndrome and forms a complex with the DNA repair proteins Rad50 and Mrel1. Here we show that phosphorylation of NBS1, induced by ionizing radiation, requires catalytically active ATM. Complexes containing ATM and NBS1 exist in vivo in both untreated cells and cells treated with ionizing radiation. We have identified two residues of NBS1, Ser 278 and Ser 343 that are phosphorylated in vitro by ATM and whose modification in vivo is essential for the cellular response to DNA damage. This response includes S-phase checkpoint activation, formation of the NBS1/Mrel1/Rad50 nuclear foci and rescue of hypersensitivity to ionizing radiation. Together, these results demonstrate a biochemical link between cell-cycle checkpoints activated by DNA damage and DNA repair in two genetic diseases with overlapping phenotypes. More... »

PAGES

473

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/35013083

DOI

http://dx.doi.org/10.1038/35013083

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1010220304

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10839544


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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.10.1038/35013083'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/35013083'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/35013083'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/35013083'


 

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