BRCTx is a novel, highly conserved RAD18-interacting protein.
The BRCT domain is a highly conserved module found in many proteins that participate in DNA damage checkpoint regulation, DNA repair, and cell cycle control. Here we describe the cloning, characterization, and targeted mutagenesis of Brctx, a novel gene with a BRCT motif. Brctx was found to be expressed ubiquitously in adult tissues and during development, with the highest levels found in testis. Brctx-deficient mice develop normally, show no pathological abnormalities, and are fertile. BRCTx binds to the C terminus of hRAD18 in yeast two-hybrid and immunoprecipitation assays and colocalizes with this protein in the nucleus. Despite this, Brctx-deficient murine embryonic fibroblasts (MEFs) do not show overt sensitivity to DNA-damaging agents. MEFs from Brctx-deficient embryos grow at a similar rate to wild-type MEF CD4/CD8 expressions, and the cell cycle parameters of thymocytes from wild-type and Brctx knockout animals are indistinguishable. Intriguingly, the BRCT domain of BRCTx is responsible for mediating its localization to the nucleus and centrosome in interphase cells. We conclude that, although highly conserved, Brctx is not essential for the above-mentioned processes and may be redundant.
Adams
David J
DJ
The Wellcome Trust Sanger Institute Hinxton, Cambs CB10 1SA, United Kingdom.
van der Weyden
Louise
L
Gergely
Fanni V
FV
Arends
Mark J
MJ
Ng
Bee Ling
BL
Tannahill
David
D
Kanaar
Roland
R
Markus
Andrea
A
Morris
Brian J
BJ
Bradley
Allan
A
D000595:Amino Acid Sequence; D000818:Animals; D001835:Body Weight; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D011485:Protein Binding; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C485954:RAD18 protein, human; D044767:Ubiquitin-Protein Ligases