کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2039488 1073061 2016 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
پیش نمایش صفحه اول مقاله
RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks
چکیده انگلیسی


• RECQL4 promotes 5′ end resection at DSBs
• RECQL4 recruitment to DSBs depends on MRE11
• RECQL4 promotes recruitment of CtIP to DSBs
• RECQL4 helicase activity is required for 5′ DNA end resection

SummaryThe RecQ helicase RECQL4, mutated in Rothmund-Thomson syndrome, regulates genome stability, aging, and cancer. Here, we identify a crucial role for RECQL4 in DNA end resection, which is the initial and an essential step of homologous recombination (HR)-dependent DNA double-strand break repair (DSBR). Depletion of RECQL4 severely reduces HR-mediated repair and 5′ end resection in vivo. RECQL4 physically interacts with MRE11-RAD50-NBS1 (MRN), which senses DSBs and initiates DNA end resection with CtIP. The MRE11 exonuclease regulates the retention of RECQL4 at laser-induced DSBs. RECQL4 also directly interacts with CtIP via its N-terminal domain and promotes CtIP recruitment to the MRN complex at DSBs. Moreover, inactivation of RECQL4’s helicase activity impairs DNA end processing and HR-dependent DSBR without affecting its interaction with MRE11 and CtIP, suggesting an important role for RECQL4’s unwinding activity in the process. Thus, we report that RECQL4 is an important participant in HR-dependent DSBR.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 16, Issue 1, 28 June 2016, Pages 161–173
نویسندگان
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