Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2

Eloïse Dray, Julia Etchin, Claudia Wiese, Dorina Saro, Gareth J. Williams, Michal Hammel, Xiong Yu, Vitold E. Galkin, Dongqing Liu, Miaw Sheue Tsai, Shirley M.H. Sy, David Schild, Edward Egelman, Junjie Chen, Patrick Sung

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

Homologous recombination mediated by RAD51 recombinase helps eliminate chromosomal lesions, such as DNA double-strand breaks induced by radiation or arising from injured DNA replication forks. The tumor suppressors BRCA2 and PALB2 act together to deliver RAD51 to chromosomal lesions to initiate repair. Here we document a new function of PALB2: to enhance RAD51's ability to form the D loop. We show that PALB2 binds DNA and physically interacts with RAD51. Notably, although PALB2 alone stimulates D-loop formation, it has a cooperative effect with RAD51AP1, an enhancer of RAD51. This stimulation stems from the ability of PALB2 to function with RAD51 and RAD51AP1 to assemble the synaptic complex. Our results demonstrate the multifaceted role of PALB2 in chromosome damage repair. Because PALB2 mutations can cause cancer or Fanconi anemia, our findings shed light on the mechanism of tumor suppression in humans.

Original languageEnglish (US)
Pages (from-to)1255-1259
Number of pages5
JournalNature Structural and Molecular Biology
Volume17
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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