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Fission yeast Ku protein is required for recovery from DNA replication stress
Author(s) -
Miyoshi Tomoichiro,
Kanoh Junko,
Ishikawa Fuyuki
Publication year - 2009
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2009.01337.x
Subject(s) - biology , ku70 , ku80 , control of chromosome duplication , dna replication , eukaryotic dna replication , replication factor c , genetics , origin recognition complex , microbiology and biotechnology , dna repair , homologous recombination , replication protein a , dna , gene , dna binding protein , transcription factor
The fundamental function of the conserved Ku70–Ku80 heterodimer is to promote the non‐homologous end‐joining (NHEJ) pathway in double‐strand break repair. Although it is thought that Ku plays several roles other than NHEJ in maintaining chromosomal integrity including telomere protection, these precise functions remain unclear. In this study, we describe a novel role of fission yeast Ku proteins encoded by pku70 + and pku80 + genes in dealing with DNA replication stress. In the absence of Rqh1, the fission yeast RecQ helicase, the cells are sensitive to reagents inducing replication stress. pku Δ rqh1 Δ double mutant showed synergistic sensitivities to these reagents. However, this synthetic phenotype was not observed when rqh1 Δ mutant was coupled with the deletion of lig4 + that encodes a ligase essential for NHEJ, indicating that the role of Ku in replication stress is NHEJ independent. pku Δ rqh1 Δ double mutant also showed highly variable copy numbers of rDNA repeats even under unstressed condition. Furthermore, the double mutant exhibited inefficient replication resumption after transient replication stalling. These results suggest the possibility that Ku proteins play an important role in genome integrity recovering replication stress.