Telomere recombination requires the MUS81 endonuclease Academic Article uri icon

Overview

MeSH Major

  • DNA-Binding Proteins
  • Endonucleases
  • Recombination, Genetic
  • Telomere

abstract

  • Telomerase-negative cancer cells maintain their telomeres through the alternative lengthening of telomeres (ALT) pathway. Although a growing body of evidence demonstrates that the ALT mechanism is a post-replicative telomere recombination process, molecular details of this pathway are largely unknown. Here we demonstrate that MUS81, a DNA structure specific recombination endonuclease, has a key role in the maintenance of telomeres in human ALT cells. We find that MUS81 specifically localizes to ALT-associated promyelocytic leukaemia (PML) nuclear bodies (APBs) and associates with telomeric DNA in ALT cells, which is enriched during the G2 phase of the cell cycle. Depletion of MUS81 results in the reduction of ALT-specific telomere recombination and leads to proliferation arrest of ALT cells. In addition, the endonuclease activity of MUS81 is required for recombination-based ALT cell survival, and the interaction of MUS81 with the telomeric repeat-binding factor TRF2 regulates this enzymatic activity, thereby maintaining telomere recombination. Thus, our results suggest that MUS81 is involved in the maintenance of ALT cell survival at least in part by homologous recombination of telomeres.

publication date

  • April 13, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2675667

Digital Object Identifier (DOI)

  • 10.1038/ncb1867

PubMed ID

  • 19363487

Additional Document Info

start page

  • 616

end page

  • 23

volume

  • 11

number

  • 5