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Cell Rep. 2016 Jun 28;16(1):161-173. doi: 10.1016/j.celrep.2016.05.079. Epub 2016 Jun 16.

RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks.

Author information

1
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
2
Center for Healthy Aging and Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.
3
Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
4
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA; Center for Healthy Aging and Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: vbohr@nih.gov.

Abstract

The 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.

KEYWORDS:

DNA repair; DNA resection; RECQL4; RecQ-like helicase; Rothmund-Thomson syndrome; homologous recombination

PMID:
27320928
PMCID:
PMC5576896
DOI:
10.1016/j.celrep.2016.05.079
[Indexed for MEDLINE]
Free PMC Article

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