Identification of S-Phase DNA Damage-Response Targets in Fission Yeast Reveals Conservation of Damage-Response Networks
Identification of S-phase DNA damage-response targets in fission yeast reveals conservation of damage-response networks Nicholas A. Willisa,1,2, Chunshui Zhoub,c,2, Andrew E. H. Eliab,d, Johanne M. Murraye, Antony M. Carre, Stephen J. Elledgeb,f,3, and Nicholas Rhinda,3 aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605; bDepartment of Genetics, Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; cThe Laboratory of Medical Genetics, Harbin Medical University, Harbin, China, 150081; dDepartment of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114; eGenome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, BN1 9RQ, United Kingdom; and fHoward Hughes Medical Institute, Harvard Medical School, Boston, MA 02115 Contributed by Stephen J. Elledge, February 16, 2016 (sent for review December 28, 2015; reviewed by Mingxia Huang and Lee Zou) The cellular response to DNA damage during S-phase regulates a Cds1 in fission yeast (11–13). Despite this plasticity in check- complicated network of processes, including cell-cycle progression, point-kinase wiring, the biological processes regulated by the gene expression, DNA replication kinetics, and DNA repair. In fission S-phase DDR are conserved. yeast, this S-phase DNA damage response (DDR) is coordinated by The S-phase DDR regulates a wide range of cellular functions, two protein kinases: Rad3, the ortholog of mammalian ATR, and including cell-cycle progression, transcription of S-phase genes, Cds1, the ortholog of mammalian Chk2. Although several critical DNA-replication kinetics, and DNA repair (14, 15). However, the downstream targets of Rad3 and Cds1 have been identified, most specific targets phosphorylated to regulate these functions have of their presumed targets are unknown, including the targets re- been identified in only a limited number of cases.
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