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  • The EMBO Journal (2006) 25, 3377 - 3388
  • doi:10.1038/sj.emboj.7601218

Published online: 29 June 2006

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

Patrick Ryan Potts1, Matthew H Porteus2,3 and Hongtao Yu1

  1. Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
  2. Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX, USA
  3. Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX, USA

Correspondence to:

Hongtao Yu, Department of Pharmacology, The University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390-9041, USA. Tel.: +1 214 645 6161; Fax: +1 214 645 6156; E-mail: hongtao.yu@utsouthwestern.edu

Matthew H Porteus, Department of Pediatrics, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9041, USA. Tel.: +1 214 648 3896; Fax: +1 214 648 3122; E-mail: matthew.porteus@utsouthwestern.edu

Received 10 May 2006; Accepted 7 June 2006

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.

  • Keywords:

    • DNA repair,
    • gene targeting,
    • MMS21,
    • sister chromatid cohesion,
    • SMC6