Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks

EMBO J. 2006 Jul 26;25(14):3377-88. doi: 10.1038/sj.emboj.7601218. Epub 2006 Jun 29.

Abstract

The structural maintenance of chromosomes (SMC) family of proteins has been implicated in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). The SMC1/3 cohesin complex is thought to promote HR by maintaining the close proximity of sister chromatids at DSBs. The SMC5/6 complex is also required for DNA repair, but the mechanism by which it accomplishes this is unclear. Here, we show that RNAi-mediated knockdown of the SMC5/6 complex components in human cells increases the efficiency of gene targeting due to a specific requirement for hSMC5/6 in sister chromatid HR. Knockdown of the hSMC5/6 complex decreases sister chromatid HR, but does not reduce nonhomologous end-joining (NHEJ) or intra-chromatid, homologue, or extrachromosomal HR. The hSMC5/6 complex is itself recruited to nuclease-induced DSBs and is required for the recruitment of cohesin to DSBs. Our results establish a mechanism by which the hSMC5/6 complex promotes DNA repair and suggest a novel strategy to improve the efficiency of gene targeting in mammalian somatic cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Cell Cycle Proteins / physiology*
  • Cell Line
  • Chondroitin Sulfate Proteoglycans / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Breakage*
  • Cohesins
  • DNA / genetics
  • DNA Damage / physiology*
  • HeLa Cells
  • Humans
  • Nuclear Proteins / metabolism*
  • Recombination, Genetic
  • Sister Chromatid Exchange / physiology*

Substances

  • Cell Cycle Proteins
  • Chondroitin Sulfate Proteoglycans
  • Chromosomal Proteins, Non-Histone
  • Nuclear Proteins
  • SMC3 protein, human
  • SMC5 protein, human
  • SMC6 protein, human
  • structural maintenance of chromosome protein 1
  • DNA