Cdc24 Is Essential for Long-range End Resection in the Repair of Double-stranded DNA Breaks*
Cdc24 Is Essential for Long-range End Resection in the Repair of Double-stranded DNA Breaks*
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DOI：
10.1074/jbc.m116.755991
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发表时间：
2016-10
期刊：
影响因子：
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通讯作者：
Huimin Zhang;Yu Hua;Rui Li;D. Kong
中科院分区：
文献类型：
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作者：
Huimin Zhang;Yu Hua;Rui Li;D. Kong
双链DNA断裂（DSB）是一种高度有害的DNA损伤，可以通过同源重组介导的修复途径进行修复。在一条DNA链上的5′到3′方向的长距离末端切除，其中3′-单链DNA突出端从断裂的DNA末端产生，是该途径中的重要步骤。DNA 2已被证明是一种必需的核酸酶在这一事件中，但DNA 2是如何招募到体内DNA断裂位点的分子机制尚未阐明。在这项研究中，一个新的重组因子Cdc 24被确定在裂殖酵母。我们证明了Cdc 24在DNA断裂修复过程中定位于DNA断裂位点，并且是长距离末端切除的重要因素。我们还确定Cdc 24通过与Dna 2和复制蛋白A（RPA）的相互作用在将Dna 2募集到DNA断裂位点中起直接作用。此外，这项研究表明，RPA作为组装机器的基础，通过其在招募Cdc 24和DNA断裂位点的重要作用，为远程末端切除。这些结果将Cdc 24定义为DSB修复中长程末端切除的重要因素，为进一步研究参与DSB修复长程末端切除的酶打开了大门。
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.