title: Cdc24 Is Essential for Long-range End Resection in the Repair of Double-stranded DNA Breaks.
abstract: 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.
authors.affiliation: From the Peking-Tsinghua Center for Life Sciences, National Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: From the Peking-Tsinghua Center for Life Sciences, National Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hua
authors.affiliation: From the Peking-Tsinghua Center for Life Sciences, National Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: From the Peking-Tsinghua Center for Life Sciences, National Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China kongdc@pku.edu.cn.
authors.forename: Daochun
authors.initials: D
authors.lastname: Kong
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000502:physiology*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D045585:Flap Endonucleases / Q000235:genetics / Q000378:metabolism; D051716:Replication Protein A / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C468288:Cdc24 protein, S pombe; D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D051716:Replication Protein A; D029702:Schizosaccharomyces pombe Proteins; C493531:Dna2 protein, S pombe; D045585:Flap Endonucleases
keywords: DNA damage; DNA endonuclease; DNA repair; DNA-protein interaction; homologous recombination