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PMID: 9736627 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells.

The EMBO journal ·Vol. 17 ·No. 18 ·1998-09-15 ·Pages 5497-508

Takata M, Sasaki MS, Sonoda E, Morrison C, Hashimoto M, Utsumi H, Yamaguchi-Iwai Y, Shinohara A, Takeda S

Abstract

Eukaryotic cells repair DNA double-strand breaks (DSBs) by at least two pathways, homologous recombination (HR) and non-homologous end-joining (NHEJ). Rad54 participates in the first recombinational repair pathway while Ku proteins are involved in NHEJ. To investigate the distinctive as well as redundant roles of these two repair pathways, we analyzed the mutants RAD54(-/-), KU70(-/-) and RAD54(-/-)/KU70(-/-), generated from the chicken B-cell line DT40. We found that the NHEJ pathway plays a dominant role in repairing gamma-radiation-induced DSBs during G1-early S phase while recombinational repair is preferentially used in late S-G2 phase. RAD54(-/-)/KU70(-/-) cells were profoundly more sensitive to gamma-rays than either single mutant, indicating that the two repair pathways are complementary. Spontaneous chromosomal aberrations and cell death were observed in both RAD54(-/-) and RAD54(-/-)/KU70(-/-) cells, with RAD54(-/-)/KU70(-/-) cells exhibiting significantly higher levels of chromosomal aberrations than RAD54(-/-) cells. These observations provide the first genetic evidence that both repair pathways play a role in maintaining chromosomal DNA during the cell cycle.

MeSH Terms
Amino Acid Sequence Animals Antigens, Nuclear B-Lymphocytes/cytology,radiation effects Cell Death Cell Line Chickens Chromosome Aberrations Cloning, Molecular DNA Helicases DNA Repair/genetics DNA-Binding Proteins/genetics,physiology Gamma Rays Interphase Ku Autoantigen Molecular Sequence Data Nuclear Proteins/genetics,physiology Radiation Tolerance Recombination, Genetic/genetics Sequence Homology, Amino Acid
Chemicals
Antigens, Nuclear DNA-Binding Proteins Nuclear Proteins DNA Helicases XRCC5 protein, human Xrcc6 protein, human Ku Autoantigen
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Takata M
Department of Molecular Immunology and Allergology, Kyoto University Medical School, Konoe Yoshida, Sakyo-ku, Kyoto 606-8315, Japan.
Sasaki M S
Sonoda E
Morrison C
Hashimoto M
Utsumi H
Yamaguchi-Iwai Y
Shinohara A
Takeda S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.18.5497
Published
1998-09-15
Pages
5497-508
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170875
Subset
IM
Databases
GENBANK
AB016529
External Links
PubMed source DOI: 10.1093/emboj/17.18.5497 PMC Full Text View journal details
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