Human MMS21/NSE2 is a SUMO ligase required for DNA repair

Patrick Ryan Potts, Hongtao Yu

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

DNA repair is required for the genomic stability and well-being of an organism. In yeasts, a multisubunit complex consisting of SMC5, SMC6, MMS21/NSE2, and other non-SMC proteins is required for DNA repair through homologous recombination. The yeast MMS21 protein is a SUMO ligase. Here we show that the human homolog of MMS21 is also a SUMO ligase. hMMS21 stimulates sumoylation of hSMC6 and the DNA repair protein TRAX. Depletion of hMMS21 by RNA interference (RNAi) sensitizes HeLa cells toward DNA damage-induced apoptosis. Ectopic expression of wild-type hMMS21, but not its ligase-inactive mutant, rescues this hypersensitivity of hMMS21-RNAi cells. ATM/ATR are hyperactivated in hMMS21-RNAi cells upon DNA damage. Consistently, hMMS21-RNAi cells show an increased number of phospho-CHK2 foci. Finally, we show that hMMS21-RNAi cells show a decreased capacity to repair DNA lesions as measured by the comet assay. Our findings suggest that the human SMC5/6 complex and the SUMO ligase activity of hMMS21 are required for the prevention of DNA damage-induced apoptosis by facilitating DNA repair in human cells.

Original languageEnglish (US)
Pages (from-to)7021-7032
Number of pages12
JournalMolecular and Cellular Biology
Volume25
Issue number16
DOIs
StatePublished - Aug 2005

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Ligases
RNA Interference
DNA Repair
DNA Damage
Apoptosis
Sumoylation
Recombinational DNA Repair
Comet Assay
Fungal Proteins
Genomic Instability
HeLa Cells
Hypersensitivity
Proteins
Yeasts

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Human MMS21/NSE2 is a SUMO ligase required for DNA repair. / Potts, Patrick Ryan; Yu, Hongtao.

In: Molecular and Cellular Biology, Vol. 25, No. 16, 08.2005, p. 7021-7032.

Research output: Contribution to journalArticle

Potts, Patrick Ryan ; Yu, Hongtao. / Human MMS21/NSE2 is a SUMO ligase required for DNA repair. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 16. pp. 7021-7032.
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