Cellular localization of human Rad51C and regulation of ubiquitin-mediated proteolysis of Rad51.
Rad51-catalyzed homologous recombination is an important pathway for repair of DNA double strand breaks and maintenance of genome integrity in vertebrate cells. Five proteins referred to as Rad51 paralogs promote Rad51 activity and are proposed to act at various, and in some cases, multiple stages in the recombination pathway. Imaging studies of native Rad51 have revealed its cellular response to DNA damage, yet visualization of the paralog proteins has met with limited success. In this study, we are able to detect endogenous Rad51C and Xrcc3 in human cells. In an effort to determine how Rad51, Rad51C, and Xrcc3 influence the pattern of localization of each other over the time course of DNA damage and repair, we have made the unexpected observation that Rad51 degradation via the ubiquitin-mediated proteasome pathway occurs as a natural part of recombinational DNA repair. Additionally, we find that Rad51C plays an important role in regulating this process. This article contains supplementary material, which may be viewed at the Journal of Cellular Biochemistry website at http://www.interscience.wiley.com/jpages/0730-2312/suppmat/index.html.
Bennett
Brian T
BT
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Aaron Lazare Medical Research Building, 364 Plantation Street, Worcester, Massachusetts 01605-2324, USA.
Knight
Kendall L
KL
D000818:Animals; D002478:Cells, Cultured; D004249:DNA Damage / Q000502:physiology / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D034741:RNA, Small Interfering / Q000378:metabolism; D051135:Rad51 Recombinase / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism* / Q000494:pharmacology
D004268:DNA-Binding Proteins; C448305:RAD51C protein, human; D034741:RNA, Small Interfering; D025801:Ubiquitin; C110901:X-ray repair cross complementing protein 3; D051135:Rad51 Recombinase