TY - JOUR
T1 - Cdc24 is essential for long-range end resection in the repair of double-stranded DNA breaks
AU - Zhang, Huimin
AU - Hua, Yu
AU - Li, Rui
AU - Kong, Daochun
N1 - Funding Information:
This work was supported by Grant 31230021 from the National Natural Science Foundation of China and Grant 2013CB911000 from the Ministry of Science and Technology of China. This work also was supported by grants from the Peking-Tsinghua Center for Life Sciences and the National Key Laboratory of Protein and Plant Gene Research. The authors declare that they have no conflicts of interest with the contents of this article. We thank Li-Lin Du and T. C. Humphrey for gifting us with the strains used in this study, M. Yanagida for the cdc24ts mutant, X. Li for help with the fluorescent assays, Y. Yu and J. Zhang for experimental advice, and the members of the Kong laboratory for their support during the course of this study.
Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2016/11/25
Y1 - 2016/11/25
N2 - Double-stranded DNA breaks (DSBs) are highly detrimental DNA lesions, which may be repaired by the homologous recombination-mediated repair pathway. The 5′ to 3′ direction of long-range end resection on one DNA strand, in which 3′-single-stranded DNA overhangs are created from broken DNA ends, is an essential step in this pathway. Dna2 has been demonstrated as an essential nuclease in this event, but the molecular mechanism of how Dna2 is recruited to DNA break sites in vivo has not been elucidated. In this study, a novel recombination factor called Cdc24 was identified in fission yeast. We demonstrated that Cdc24 localizes to DNA break sites during the repair of DNA breaks and is an essential factor in long-range end resection. We also determined that Cdc24 plays a direct role in recruiting Dna2 to DNA break sites through its interaction with Dna2 and replication protein A (RPA). Further, this study revealed that RPA acts as the foundation for assembling the machinery for long-range end resection by its essential role in recruiting Cdc24 and Dna2 to DNA break sites. These results define Cdc24 as an essential factor for long-range end resection in the repair of DSBs, opening the door for further investigations into the enzymes involved in long-range end resection for DSB repair.
AB - Double-stranded DNA breaks (DSBs) are highly detrimental DNA lesions, which may be repaired by the homologous recombination-mediated repair pathway. The 5′ to 3′ direction of long-range end resection on one DNA strand, in which 3′-single-stranded DNA overhangs are created from broken DNA ends, is an essential step in this pathway. Dna2 has been demonstrated as an essential nuclease in this event, but the molecular mechanism of how Dna2 is recruited to DNA break sites in vivo has not been elucidated. In this study, a novel recombination factor called Cdc24 was identified in fission yeast. We demonstrated that Cdc24 localizes to DNA break sites during the repair of DNA breaks and is an essential factor in long-range end resection. We also determined that Cdc24 plays a direct role in recruiting Dna2 to DNA break sites through its interaction with Dna2 and replication protein A (RPA). Further, this study revealed that RPA acts as the foundation for assembling the machinery for long-range end resection by its essential role in recruiting Cdc24 and Dna2 to DNA break sites. These results define Cdc24 as an essential factor for long-range end resection in the repair of DSBs, opening the door for further investigations into the enzymes involved in long-range end resection for DSB repair.
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U2 - 10.1074/jbc.M116.755991
DO - 10.1074/jbc.M116.755991
M3 - Article
C2 - 27729451
AN - SCOPUS:84997830809
SN - 0021-9258
VL - 291
SP - 24961
EP - 24973
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 48
ER -