Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells

Akira Fujimori, Seiji Tachiiri, Eiichiro Sonoda, Larry H. Thompson, Pawan Kumar Dhar, Masahiro Hiraoka, Shunichi Takeda, Yong Zhang, Michael Reth, Minoru Takata

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Yeast Rad52 DNA-repair mutants exhibit pronounced radiation sensitivity and a defect in homologous recombination (HR), whereas vertebrate cells lacking Rad52 exhibit a nearly normal phenotype. Biochemical studies show that both yeast Rad52 and Rad55-57 (Rad51 paralogs) stimulate DNA-strand exchange mediated by Rad51. These findings raise the possibility that Rad51 paralogs may compensate for lack of Rad52 in vertebrate cells, explaining the absence of prominent phenotypes for Rad52-deficient cells. To test this hypothesis, using chicken DT40 cells, we generated conditional mutants deficient in both RAD52 and XRCC3, which is one of the five vertebrate RAD51 paralogs. Surprisingly, the rad52 xrcc3 double-mutant cells were non-viable and exhibited extensive chromosomal breaks, whereas rad52 and xrcc3 single mutants grew well. Our data reveal an overlapping (but non-reciprocal) role for Rad52 and XRCC3 in repairing DNA double-strand breaks. The present study shows that Rad52 can play an important role in HR repair by partially substituting for a Rad51 paralog.

Original languageEnglish (US)
Pages (from-to)5513-5520
Number of pages8
JournalEMBO Journal
Volume20
Issue number19
DOIs
StatePublished - Oct 1 2001
Externally publishedYes

Fingerprint

Vertebrates
Yeast
DNA
Repair
Yeasts
Phenotype
Recombinational DNA Repair
Chromosome Breakage
Double-Stranded DNA Breaks
Radiation Tolerance
Homologous Recombination
Radiation
Defects
DNA Repair
Chickens

Keywords

  • DT40
  • Homologous recombination
  • Rad51 paralogs
  • Rad52
  • XRCC3

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Fujimori, A., Tachiiri, S., Sonoda, E., Thompson, L. H., Dhar, P. K., Hiraoka, M., ... Takata, M. (2001). Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells. EMBO Journal, 20(19), 5513-5520. https://doi.org/10.1093/emboj/20.19.5513

Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells. / Fujimori, Akira; Tachiiri, Seiji; Sonoda, Eiichiro; Thompson, Larry H.; Dhar, Pawan Kumar; Hiraoka, Masahiro; Takeda, Shunichi; Zhang, Yong; Reth, Michael; Takata, Minoru.

In: EMBO Journal, Vol. 20, No. 19, 01.10.2001, p. 5513-5520.

Research output: Contribution to journalArticle

Fujimori, A, Tachiiri, S, Sonoda, E, Thompson, LH, Dhar, PK, Hiraoka, M, Takeda, S, Zhang, Y, Reth, M & Takata, M 2001, 'Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells', EMBO Journal, vol. 20, no. 19, pp. 5513-5520. https://doi.org/10.1093/emboj/20.19.5513
Fujimori, Akira ; Tachiiri, Seiji ; Sonoda, Eiichiro ; Thompson, Larry H. ; Dhar, Pawan Kumar ; Hiraoka, Masahiro ; Takeda, Shunichi ; Zhang, Yong ; Reth, Michael ; Takata, Minoru. / Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells. In: EMBO Journal. 2001 ; Vol. 20, No. 19. pp. 5513-5520.
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