BRCTx is a novel, highly conserved RAD18-interacting protein

David J Adams, Louise van der Weyden, Fanni V Gergely, Mark J Arends, Bee Ling Ng, David Tannahill, Roland Kanaar, Andrea Markus, Brian J Morris, Allan Bradley

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)779-88
Number of pages10
JournalMolecular and Cellular Biology
Volume25
Issue number2
DOIs
Publication statusPublished - Jan 2005

Keywords

  • Amino Acid Sequence
  • Animals
  • Body Weight
  • Carrier Proteins
  • Cell Cycle
  • Cells, Cultured
  • Centrosome
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins
  • Fibroblasts
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Nuclear Proteins
  • Organ Size
  • Protein Binding
  • Sequence Alignment
  • T-Lymphocytes
  • Testis
  • Tissue Distribution
  • Two-Hybrid System Techniques

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