A role for SSRP1 in recombination-mediated DNA damage response

Anuradha Kumari, Olga M. Mazina, Ujwal Shinde, Alexander V. Mazin, Hua Lu

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

A possible role for structure-specific recognition protein 1 (SSRP1) in replication-associated repair processes has previously been suggested based on its interaction with several DNA repair factors and the replication defects observed in SSRP1 mutants. In this study, we investigated the potential role of SSRP1 in association with DNA repair mediated by homologous recombination (HR), one of the pathways involved in repairing replication-associated DNA damage, in mammalian cells. Surprisingly, over-expression of SSRP1 reduced the number of hprt+ recombinants generated via HR both spontaneously and upon hydroxyurea (HU) treatment, whereas knockdown of SSRP1 resulted in an increase of HR events in response to DNA double-strand break formation. In correlation, we found that the depletion of SSRP1 in HU-treated human cells elevated the number of Rad51 and H2AX foci, while over-expression of the wild-type SSRP1 markedly reduced HU-induced Rad51 foci formation. We also found that SSRP1 physically interacts with a key HR repair protein, Rad54 both in vitro and in vivo. Further, branch migration studies demonstrated that SSRP1 inhibits Rad54-promoted branch migration of Holliday junctions in vitro. Taken together, our data suggest a functional role for SSRP1 in spontaneous and replication-associated DNA damage response by suppressing avoidable HR repair events.

Original languageEnglish (US)
Pages (from-to)508-518
Number of pages11
JournalJournal of Cellular Biochemistry
Volume108
Issue number2
DOIs
StatePublished - Oct 1 2009

Fingerprint

Genetic Recombination
DNA Damage
DNA
Proteins
Recombinational DNA Repair
Repair
Hydroxyurea
Homologous Recombination
Cruciform DNA
Cells
Double-Stranded DNA Breaks
Mutant Proteins
DNA Repair
Cell Count
Defects

Keywords

  • Branch migration
  • DNA damage repair
  • Homologous recombination
  • Rad54
  • SSRP1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

A role for SSRP1 in recombination-mediated DNA damage response. / Kumari, Anuradha; Mazina, Olga M.; Shinde, Ujwal; Mazin, Alexander V.; Lu, Hua.

In: Journal of Cellular Biochemistry, Vol. 108, No. 2, 01.10.2009, p. 508-518.

Research output: Contribution to journalArticle

Kumari, Anuradha ; Mazina, Olga M. ; Shinde, Ujwal ; Mazin, Alexander V. ; Lu, Hua. / A role for SSRP1 in recombination-mediated DNA damage response. In: Journal of Cellular Biochemistry. 2009 ; Vol. 108, No. 2. pp. 508-518.
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