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SLX4 assembles a telomere maintenance toolkit by bridging multiple endonucleases with telomeres.

TitleSLX4 assembles a telomere maintenance toolkit by bridging multiple endonucleases with telomeres.
Publication TypeJournal Article
Year of Publication2013
AuthorsWan B, Yin J, Horvath K, Sarkar J, Chen Y, Wu J, Wan K, Lu J, Gu P, Yu EYoung, Lue NF, Chang S, Liu Y, Lei M
JournalCell Rep
Volume4
Issue5
Pagination861-9
Date Published2013 Sep 12
ISSN2211-1247
KeywordsDNA Repair, Endonucleases, Humans, Recombinases, Telomere
Abstract

SLX4 interacts with several endonucleases to resolve structural barriers in DNA metabolism. SLX4 also interacts with telomeric protein TRF2 in human cells. The molecular mechanism of these interactions at telomeres remains unknown. Here, we report the crystal structure of the TRF2-binding motif of SLX4 (SLX4TBM) in complex with the TRFH domain of TRF2 (TRF2TRFH) and map the interactions of SLX4 with endonucleases SLX1, XPF, and MUS81. TRF2 recognizes a unique HxLxP motif on SLX4 via the peptide-binding site in its TRFH domain. Telomeric localization of SLX4 and associated nucleases depend on the SLX4-endonuclease and SLX4-TRF2 interactions and the protein levels of SLX4 and TRF2. SLX4 assembles an endonuclease toolkit that negatively regulates telomere length via SLX1-catalyzed nucleolytic resolution of telomere DNA structures. We propose that the SLX4-TRF2 complex serves as a double-layer scaffold bridging multiple endonucleases with telomeres for recombination-based telomere maintenance.

DOI10.1016/j.celrep.2013.08.017
Alternate JournalCell Rep
PubMed ID24012755
PubMed Central IDPMC4334113
Grant List / / Howard Hughes Medical Institute / United States
R01 CA129037 / CA / NCI NIH HHS / United States
ZIA AG000754-01 / / Intramural NIH HHS / United States

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