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Genes to Cells (2009) 14, 1091-1103. doi:10.1111/j.1365-2443.2009.01337.x
© 2009 Blackwell Publishing or its licensors

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Fission yeast Ku protein is required for recovery from DNA replication stress

Tomoichiro Miyoshia, Junko Kanohb and Fuyuki Ishikawa*

Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan

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{Delta}rqh1{Delta} double mutant showed synergistic sensitivities to these reagents. However, this synthetic phenotype was not observed when rqh1{Delta} 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{Delta}rqh1{Delta} 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.


Communicated by: Eisuke Nishida

aPresent address: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba 3-8-1, Meguro-ku, Tokyo 153-8902, Japan.

bPresent address: Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.

* fishikaw{at}lif.kyoto-u.ac.jp







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