Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2
Dray, Eloise, 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 (2010) Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2. Nature Structural & Molecular Biology, 17(10), pp. 1255-1259.
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.
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|Item Type:||Journal Article|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL BIOCHEMISTRY AND METABOLOMICS (110100)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL MICROBIOLOGY (110800)
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2010 Nature Publishing Group|
|Deposited On:||03 Jul 2014 00:55|
|Last Modified:||03 Jul 2014 23:11|
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