Promotion of Dnl4-Catalyzed DNA end-joining by the Rad50/Mre11/Xrs2 and Hdf1/Hdf2 complexes

Ling Chen, Kelly Trujillo, William Ramos, Patrick Sung, Alan E. Tomkinson

Research output: Contribution to journalArticle

238 Scopus citations

Abstract

S. cerevisiae RAD50, MRE11, and XRS2 genes are required for telomere maintenance, cell cycle checkpoint signaling, meiotic recombination, and the efficient repair of DNA double-strand breaks (DSB)s by homologous recombination and nonhomologous end-joining (NHEJ). Here, we demonstrate that the complex formed by Rad50, Mre11, and Xrs2 proteins promotes intermolecular DNA joining by DNA ligase IV (Dnl4) and its associated protein Lif1. Our results show that the Rad50/Mre11/Xrs2 complex juxtaposes linear DNA molecules via their ends to form oligomers and interacts directly with Dnl4/Lif1. We also demonstrate that Rad50/Mre11/Xrs2-mediated intermolecular DNA joining is further stimulated by Hdf1/Hdf2, the yeast homolog of the mammalian Ku70/Ku80 heterodimer. These studies reveal specific functional interplay among the Hdf1/Hdf2, Rad50/Mre11/Xrs2, and Dnl4/Lif1 complexes in NHEJ.

Original languageEnglish (US)
Pages (from-to)1105-1115
Number of pages11
JournalMolecular Cell
Volume8
Issue number5
DOIs
StatePublished - Nov 21 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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