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Single-Strand Break End Resection in Genome Integrity: Mechanism and Regulation by APE2

Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28223, USA
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Int. J. Mol. Sci. 2018, 19(8), 2389; https://doi.org/10.3390/ijms19082389
Received: 19 June 2018 / Revised: 7 August 2018 / Accepted: 11 August 2018 / Published: 14 August 2018
(This article belongs to the Special Issue DNA Replication Stress)
DNA single-strand breaks (SSBs) occur more than 10,000 times per mammalian cell each day, representing the most common type of DNA damage. Unrepaired SSBs compromise DNA replication and transcription programs, leading to genome instability. Unrepaired SSBs are associated with diseases such as cancer and neurodegenerative disorders. Although canonical SSB repair pathway is activated to repair most SSBs, it remains unclear whether and how unrepaired SSBs are sensed and signaled. In this review, we propose a new concept of SSB end resection for genome integrity. We propose a four-step mechanism of SSB end resection: SSB end sensing and processing, as well as initiation, continuation, and termination of SSB end resection. We also compare different mechanisms of SSB end resection and DSB end resection in DNA repair and DNA damage response (DDR) pathways. We further discuss how SSB end resection contributes to SSB signaling and repair. We focus on the mechanism and regulation by APE2 in SSB end resection in genome integrity. Finally, we identify areas of future study that may help us gain further mechanistic insight into the process of SSB end resection. Overall, this review provides the first comprehensive perspective on SSB end resection in genome integrity. View Full-Text
Keywords: APE2; ATR-Chk1 DDR pathway; Genome integrity; SSB end resection; SSB repair; SSB signaling APE2; ATR-Chk1 DDR pathway; Genome integrity; SSB end resection; SSB repair; SSB signaling
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Hossain, M.A.; Lin, Y.; Yan, S. Single-Strand Break End Resection in Genome Integrity: Mechanism and Regulation by APE2. Int. J. Mol. Sci. 2018, 19, 2389.

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