A Critical Role for the Ubiquitin-Conjugating Enzyme Ubc13 in Initiating Homologous Recombination

Guang Yu Zhao, Eiichiro Sonoda, Louise J. Barber, Hayato Oka, Yasuhiro Murakawa, Kouichi Yamada, Tsuyoshi Ikura, Xin Wang, Masahiko Kobayashi, Kenichi Yamamoto, Simon J. Boulton, Shunichi Takeda

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

The ubiquitin (Ub)-conjugating enzyme Ubc13 is implicated in Rad6/Rad18-dependent postreplication repair (PRR) in budding yeast, but its function in vertebrates is not known. We show here that disruption or siRNA depletion of UBC13 in chicken DT40 or human cells confers severe growth defects due to chromosome instability, and hypersensitivity to both UV and ionizing radiation, consistent with a conserved role for Ubc13 in PRR. Remarkably, Ubc13-deficient cells are also compromised for DNA double-strand break (DSB) repair by homologous recombination (HR). Recruitment and activation of the E3 Ub ligase function of BRCA1 and the subsequent formation of the Rad51 nucleoprotein filament at DSBs are abolished in Ubc13-deficient cells. Furthermore, generation of ssDNA/RPA complexes at DSBs is severely attenuated in the absence of Ubc13. These data reveal a critical and unexpected role for vertebrate Ubc13 in the initiation of HR at the level of DSB processing.

Original languageEnglish
Pages (from-to)663-675
Number of pages13
JournalMolecular Cell
Volume25
Issue number5
DOIs
Publication statusPublished - Mar 9 2007
Externally publishedYes

    Fingerprint

Keywords

  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Zhao, G. Y., Sonoda, E., Barber, L. J., Oka, H., Murakawa, Y., Yamada, K., Ikura, T., Wang, X., Kobayashi, M., Yamamoto, K., Boulton, S. J., & Takeda, S. (2007). A Critical Role for the Ubiquitin-Conjugating Enzyme Ubc13 in Initiating Homologous Recombination. Molecular Cell, 25(5), 663-675. https://doi.org/10.1016/j.molcel.2007.01.029