Disparate requirements for the Walker A and B ATPase motifs ofhuman RAD51D in homologous recombination

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In vertebrates, homologous recombinational repair (HRR) requires RAD51 and five RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C, and RAD51D) that all contain conserved Walker A and B ATPase motifs. In human RAD51D we examined the requirement for these motifs in interactions with XRCC2 and RAD51C, and for survival of cells in response to DNA interstrand crosslinks. Ectopic expression of wild type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line. Although A-motif mutants complement very efficiently, B-motif mutants do not. Consistent with these results, experiments ... continued below

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Wiese, Claudia; Hinz, John M.; Tebbs, Robert S.; Nham, Peter B.; Urbin, Salustra S.; Collins, David W. et al. April 21, 2006.

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In vertebrates, homologous recombinational repair (HRR) requires RAD51 and five RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C, and RAD51D) that all contain conserved Walker A and B ATPase motifs. In human RAD51D we examined the requirement for these motifs in interactions with XRCC2 and RAD51C, and for survival of cells in response to DNA interstrand crosslinks. Ectopic expression of wild type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line. Although A-motif mutants complement very efficiently, B-motif mutants do not. Consistent with these results, experiments using the yeast two- and three-hybrid systems show that the interactions between RAD51D and its XRCC2 and RAD51C partners also require a functional RAD51D B motif, but not motif A. Similarly, hamster Xrcc2 is unable to bind to the non-complementing human RAD51D B-motif mutants in co-immunoprecipitation assays. We conclude that a functional Walker B motif, but not A motif, is necessary for RAD51D's interactions with other paralogs and for efficient HRR. We present a model in which ATPase sites are formed in a bipartite manner between RAD51D and other RAD51 paralogs.

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  • Journal Name: Nucleic Acids Research; Journal Volume: 34; Journal Issue: 9; Related Information: Journal Publication Date: 2006

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  • Report No.: LBNL--60062
  • Grant Number: DE-AC02-05CH11231
  • Grant Number: NASA:NNJ05HI36I, NIH:P01CA92584
  • DOI: 10.1093/nar/gkl366 | External Link
  • Office of Scientific & Technical Information Report Number: 901820
  • Archival Resource Key: ark:/67531/metadc888729

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  • April 21, 2006

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  • Sept. 22, 2016, 2:13 a.m.

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  • Dec. 15, 2016, 1:25 p.m.

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Wiese, Claudia; Hinz, John M.; Tebbs, Robert S.; Nham, Peter B.; Urbin, Salustra S.; Collins, David W. et al. Disparate requirements for the Walker A and B ATPase motifs ofhuman RAD51D in homologous recombination, article, April 21, 2006; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc888729/: accessed November 21, 2017), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.