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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2.

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

Published In Nat Struct Mol Biol, (2010 Oct)

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.

PubMed ID: 20871616 Exiting the NIEHS site

MeSH Terms: Apoptosis Regulatory Proteins; BRCA2 Protein/chemistry; BRCA2 Protein/physiology*; Breast Neoplasms/metabolism*; DNA Repair/physiology*; DNA, Neoplasm/metabolism*; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/physiology*; Fanconi Anemia Complementation Group N Protein; Female; Humans; Multiprotein Complexes; Neoplasm Proteins/chemistry; Neoplasm Proteins/physiology*; Nuclear Proteins/chemistry; Nuclear Proteins/genetics; Nuclear Proteins/physiology*; Peptide Fragments/metabolism; Protein Binding; Protein Interaction Mapping; Rad51 Recombinase/chemistry; Rad51 Recombinase/physiology*; Recombinant Fusion Proteins/chemistry; Recombinant Fusion Proteins/physiology; Recombination, Genetic/physiology*; Tumor Suppressor Proteins/chemistry; Tumor Suppressor Proteins/genetics; Tumor Suppressor Proteins/physiology*

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