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

Bingbing Wan, Jinhu Yin, Kent Horvath, Jaya Sarkar, Yong Chen, Jian Wu, Ke Wan, Jian Lu, Peili Gu, Eun Young Yu, Neal F. Lue, Sandy Chang, Yie Liu, Ming Lei

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish (US)
Pages (from-to)861-869
Number of pages9
JournalCell Reports
Volume4
Issue number5
DOIs
StatePublished - May 12 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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