The forkhead-associated domain of NBS1 is essential for nuclear foci formation after irradiation but not essential for hRAD50·hMRE11·-NBS1 complex DNA repair activity

Hiroshi Tauchi, Junya Kobayashii, Ken Ichi Morishima, Shinya Matsuura, Asako Nakamura, Takahiro Shiraishi, Emi Ito, Debora Masnada, Domenico Delia, Kenshi Komatsu

Research output: Contribution to journalArticlepeer-review

Abstract

NBS1 (p95), the protein responsible for Nijmegen breakage syndrome, shows a weak homology to the yeast Xrs2 protein at the N terminus region, known as the forkhead-associated (FHA) domain and the BRCA1 C terminus domain. The protein interacts with hMRE11 to form a complex with a nuclease activity for initiation of both nonhomologous end joining and homologous recombination. Here, we show in vivo direct evidence that NBS1 recruits the hMRE11 nuclease complex into the cell nucleus and leads to the formation of foci by utilizing different functions from several domains. The amino acid sequence at 665-693 on the C terminus of NBS1, where a novel identical sequence with yeast Xrs2 protein was found, is essential for hMRE11 binding. The hMRE11-binding region is necessary for both nuclear localization of the complex and for cellular radiation resistance. On the other hand, the FHA domain regulates nuclear loci formation of the multiprotein complex in response to DNA damage but is not essential for nuclear transportation of the complex and radiation resistance. Because the FHA/BRCA1 C terminus domain is widely conserved in eukaryotic nuclear proteins related to the cell cycle, gene regulation, and DNA repair, the loci formation could be associated with many phenotypes of Nijmegen breakage syndrome other than radiation sensitivity.

Original languageEnglish
Pages (from-to)12-15
Number of pages4
JournalJournal of Biological Chemistry
Volume276
Issue number1
DOIs
Publication statusPublished - Jan 5 2001

ASJC Scopus subject areas

  • Biochemistry

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