Distinct BRCT domains in Mcph1/Brit1 mediate ionizing radiation-induced focus formation and centrosomal localization

Jeffers, L J and Coull, B J and Stack, S J and Morrison, C G (2008) Distinct BRCT domains in Mcph1/Brit1 mediate ionizing radiation-induced focus formation and centrosomal localization. Oncogene, 27 (1). pp. 139-144. ISSN 0950-9232

Full text not available from this repository.

Abstract

Microcephalin (MCPH1/BRIT1) forms ionizing radiation-induced nuclear foci (IRIF) and is required for DNA damage-responsive S and G(2)-M-phase checkpoints. MCPH1 contains three BRCT domains. Here we report the cloning of chicken Mcph1 (cMcph1) and functional analysis of its individual BRCT domains. Full-length cMcph1 localized to centrosomes throughout the cell cycle and formed IRIF that colocalized with gamma-H2AX. The tandem C-terminal BRCT2 and BRCT3 domains of cMcph1 were necessary for IRIF formation, while the N-terminal BRCT1 was required for centrosomal localization in irradiated cells. Centrosomal targeting of cMcph1 was independent of ATM, Brca1 or Chk1. cMcph1 formed IRIF in ATM- and Brca1-deficient cells, but not in H2AX-deficient cells. Inability to form cMcph1 IRIF impaired the cellular response to DNA damage. These results suggest that the role of microcephalin in the vertebrate DNA damage response is controlled by interaction of the C-terminal BRCT domains with gamma-H2AX.

Item Type:
Journal Article
Journal or Publication Title:
Oncogene
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1306
Subjects:
ID Code:
136256
Deposited By:
Deposited On:
21 Aug 2019 13:15
Refereed?:
Yes
Published?:
Published
Last Modified:
05 Aug 2020 08:01