Actions for Nonenzymatic Role for WRN in Preserving Nascent DNA Strands after Replication Stress [electronic resource].

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Nonenzymatic Role for WRN in Preserving Nascent DNA Strands after Replication Stress [electronic resource].

Published
Washington, D.C. : United States. Dept. of Energy, 2014.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy
Physical Description
pages 1,387-1,401 : digital, PDF file
Additional Creators
Lawrence Berkeley National Laboratory, United States. Department of Energy, National Institutes of Health (U.S.), National Aeronautics and Space Administration Announcement, and United States. Department of Energy. Office of Scientific and Technical Information
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Summary
WRN, the protein defective in Werner syndrome (WS), is a multifunctional nuclease involved in DNA damage repair, replication, and genome stability maintenance. It was assumed that the nuclease activities of WRN were critical for these functions. Here, we report a nonenzymatic role for WRN in preserving nascent DNA strands following replication stress. We found that lack of WRN led to shortening of nascent DNA strands after replication stress. Furthermore, we discovered that the exonuclease activity of MRE11 was responsible for the shortening of newly replicated DNA in the absence of WRN. Mechanistically, the N-terminal FHA domain of NBS1 recruits WRN to replication-associated DNA double-stranded breaks to stabilize Rad51 and to limit the nuclease activity of its C-terminal binding partner MRE11. Thus, this previously unrecognized nonenzymatic function of WRN in the stabilization of nascent DNA strands sheds light on the molecular reason for the origin of genome instability in WS individuals.
Report Numbers
E 1.99:1207937
Subject(s)
Note
Published through SciTech Connect.
11/20/2014.
": S2211124714008791"
Cell Reports 9 4 ISSN 2211-1247 AM
Su, Fengtao; Mukherjee, Shibani; Yang, Yanyong; Mori, Eiichiro; Bhattacharya, Souparno; Kobayashi, Junya; Yannone, Steven ; Chen, David ; Asaithamby, Aroumougame.
Funding Information
AC02-05CH11231
View MARC record | catkey: 23498685