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PMID: 8052631 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Involvement of the Ku autoantigen in the cellular response to DNA double-strand breaks.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 16 ·1994-08-02 ·Pages 7623-7

Rathmell WK, Chu G

Abstract

The Ku autoantigen is a well-characterized heterodimer of 70 and 86 kDa that binds to DNA ends, but its cellular function has been obscure. An electrophoretic mobility-shift assay and Ku antisera were used to show that Ku or a closely related protein was deficient in three mutant hamster cell lines from x-ray-sensitive complementation group 5, which is characterized by defects in DNA double-strand break repair and V(D)J recombination. Furthermore, Ku protein expression was restored when the cells reverted to x-ray resistance. The Ku p86 gene maps to human chromosome 2q33-35, and group 5 cells are rescued by almost precisely the same region, 2q34-36. Thus, biochemical and genetic evidence suggests that Ku is involved in pathways for DNA recombination and repair. By its association with a DNA-dependent protein kinase activated by DNA ends, Ku may also initiate a signaling pathway induced by DNA damage, perhaps for cell cycle arrest.

MeSH Terms
Animals Antigens, Nuclear Autoantigens/genetics,immunology,metabolism Cells, Cultured Chromosomes, Human, Pair 2 Cricetinae DNA Damage DNA Helicases DNA Repair DNA-Binding Proteins/genetics,immunology,metabolism Humans Ku Autoantigen Nuclear Proteins/genetics,immunology,metabolism Radiation Tolerance Recombination, Genetic X-Rays
Chemicals
Antigens, Nuclear Autoantigens DNA-Binding Proteins Nuclear Proteins DNA Helicases XRCC5 protein, human Xrcc6 protein, human Ku Autoantigen
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Rathmell W K
Department of Medicine, Stanford University School of Medicine, CA 94305.
Chu G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.16.7623
Published
1994-08-02
Pages
7623-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44454
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.91.16.7623 PMC Full Text View journal details
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