Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl

Nan Wu, Xiangduo Kong, Zhejian Ji, Weihua Zeng, Patrick Ryan Potts, Kyoko Yokomori, Hongtao Yu

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

DNA double-strand br eaks (DSBs) fuel cancer-driving chromosome translocations. Two related structural maintenance of chromosomes (Smc) complexes, cohesin and Smc5/6, promote DSB repair through sister chromatid homologous recombination (SCR). Here we show that the Smc5/6 subunit Mms21 sumoylates multiple lysines of the cohesin subunit Scc1. Mms21 promotes cohesin-dependent small ubiquitin-like modifier (SUMO) accumulation at laser-induced DNA damage sites in S/G2 human cells. Cells expressing the nonsumoylatable Scc1 mutant (15KR) maintain sister chromatid cohesion during mitosis but are defective in SCR and sensitive to ionizing radiation (IR). Scc1 15KR is recruited to DNA damage sites. Depletion of Wapl, a negative cohesin regulator, rescues SCR defects of Mms21-deficient or Scc1 15KR-expressing cells. Expression of the acetylationmimicking Smc3 mutant does not bypass the requirement for Mms21 in SCR. We propose that Scc1 sumoylation by Mms21 promotes SCR by antagonizing Wapl at a step after cohesin loading at DSBs and in a way not solely dependent on Smc3 acetylation.

Original languageEnglish (US)
Pages (from-to)1473-1485
Number of pages13
JournalGenes and Development
Volume26
Issue number13
DOIs
StatePublished - 2012

Fingerprint

Sumoylation
Chromatids
Homologous Recombination
Genetic Recombination
DNA Damage
Chromosomes
Acetylation
Ubiquitin
Ionizing Radiation
Mitosis
Lysine
Lasers
Maintenance
cohesins
DNA
1,2-di-(4-sulfamidophenyl)-4-butylpyrazolidine-3,5-dione
Neoplasms

Keywords

  • Cohesin
  • DNA repair
  • Smc5
  • Smc6
  • SUMO

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl. / Wu, Nan; Kong, Xiangduo; Ji, Zhejian; Zeng, Weihua; Potts, Patrick Ryan; Yokomori, Kyoko; Yu, Hongtao.

In: Genes and Development, Vol. 26, No. 13, 2012, p. 1473-1485.

Research output: Contribution to journalArticle

Wu, Nan ; Kong, Xiangduo ; Ji, Zhejian ; Zeng, Weihua ; Potts, Patrick Ryan ; Yokomori, Kyoko ; Yu, Hongtao. / Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl. In: Genes and Development. 2012 ; Vol. 26, No. 13. pp. 1473-1485.
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