Enhancement of the 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; Egelman, Edward; Chen, Junjie; Sung, Patrick; Schild, D

doi:10.2172/993859

Title: Enhancement of the RAD51 Recombinase Activity by the Tumor Suppressor PALB2

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Abstract

Homologous recombination mediated by the RAD51 recombinase helps eliminate chromosomal lesions, such as DNA double-stranded 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 in the enhancement of RAD51's ability to form the D-loop. We show that PALB2 binds DNA and physically interacts with RAD51. Importantly, while PALB2 alone stimulates D-loop formation, a cooperative effect is seen with RAD51AP1, an enhancer of RAD51. This stimulation stems from PALB2's ability to function with RAD51 and RAD51AP1 to assemble the synaptic complex. Our results help unveil a multi-faceted role of PALB2 in chromosome damage repair. Since PALB2 mutations can cause breast and other tumors or lead to Fanconi anemia, our findings are important for understanding the mechanism of tumor suppression in humans.

Authors:: 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; Egelman, Edward; Chen, Junjie; Sung, Patrick; Schild, D

Publication Date:: Tue Aug 24 00:00:00 EDT 2010

Research Org.:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Org.:: Life Sciences Division

OSTI Identifier:: 993859

Report Number(s):: LBNL-4015E
TRN: US201101%%237

DOE Contract Number:: DE-AC02-05CH11231

Resource Type:: Technical Report

Country of Publication:: United States

Language:: English

Subject:: 59; CHROMOSOMES; DNA; DNA REPLICATION; MAMMARY GLANDS; MUTATIONS; NEOPLASMS; RADIATIONS; RECOMBINATION; REPAIR; STIMULATION

Citation Formats


                    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, Egelman, Edward, Chen, Junjie, Sung, Patrick, and Schild, D. Enhancement of the RAD51 Recombinase Activity by the Tumor Suppressor PALB2.  United States: N. p., 2010. 
        Web.  doi:10.2172/993859.

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                    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, Egelman, Edward, Chen, Junjie, Sung, Patrick, & Schild, D. Enhancement of the RAD51 Recombinase Activity by the Tumor Suppressor PALB2.  United States.  https://doi.org/10.2172/993859

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                    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, Egelman, Edward, Chen, Junjie, Sung, Patrick, and Schild, D. 2010.  
        "Enhancement of the RAD51 Recombinase Activity by the Tumor Suppressor PALB2".  United States.  https://doi.org/10.2172/993859.  https://www.osti.gov/servlets/purl/993859.

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@article{osti_993859,

  title        = {Enhancement of the RAD51 Recombinase Activity by the Tumor Suppressor PALB2},

  author       = {Dray, Eloise and Etchin, Julia and Wiese, Claudia and Saro, Dorina and Williams, Gareth J and Hammel, Michal and Yu, Xiong and Galkin, Vitold E and Liu, Dongqing and Tsai, Miaw-Sheue and Sy, Shirley M-H and Egelman, Edward and Chen, Junjie and Sung, Patrick and Schild, D},

  abstractNote = {Homologous recombination mediated by the RAD51 recombinase helps eliminate chromosomal lesions, such as DNA double-stranded 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 in the enhancement of RAD51's ability to form the D-loop. We show that PALB2 binds DNA and physically interacts with RAD51. Importantly, while PALB2 alone stimulates D-loop formation, a cooperative effect is seen with RAD51AP1, an enhancer of RAD51. This stimulation stems from PALB2's ability to function with RAD51 and RAD51AP1 to assemble the synaptic complex. Our results help unveil a multi-faceted role of PALB2 in chromosome damage repair. Since PALB2 mutations can cause breast and other tumors or lead to Fanconi anemia, our findings are important for understanding the mechanism of tumor suppression in humans.},

  doi          = {10.2172/993859},

  url          = {https://www.osti.gov/biblio/993859},
  journal      = {},
number       = ,

  volume       = ,

  place        = {United States},

  year         = {Tue Aug 24 00:00:00 EDT 2010},

  month        = {Tue Aug 24 00:00:00 EDT 2010}

}

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