Premium
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
Author(s) -
Takata Minoru,
Sasaki Masao S.,
Sonoda Eiichiro,
Morrison Ciaran,
Hashimoto Mitsumasa,
Utsumi Hiroshi,
YamaguchiIwai Yuko,
Shinohara Akira,
Takeda Shunichi
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.18.5497
Subject(s) - ku70 , biology , homologous recombination , non homologous end joining , dna repair , ku80 , dna repair protein xrcc4 , microbiology and biotechnology , homology directed repair , genetics , dna , nucleotide excision repair , gene , dna binding protein , transcription factor
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 γ‐radiation‐induced DSBs during G 1 –early S phase while recombinational repair is preferentially used in late S–G 2 phase. RAD54 −/− /KU70 −/− cells were profoundly more sensitive to γ‐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.