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J Biol Chem. 2004 Aug 13;279(33):34091-4. Epub 2004 Jun 25.

Microcephalin is a DNA damage response protein involved in regulation of CHK1 and BRCA1.

Author information

1
Department of Pathology, School of Medicine, Yale University, 310 Cedar Street, New Haven, CT 06510, USA. xaxu@coh.org

Abstract

Microcephalin (MCPH1) is the first gene identified among at least six loci that contribute to the autosomal recessive disease, primary microcephaly. MCPH1, like NFBD1/MDC1, 53BP1, and BRCA1, encodes a protein with twin carboxyl-terminal BRCT domains (PTCB). Here, we report that Mcph1 forms ionizing radiation-induced foci. Down-regulation of Mcph1, like other PTCBs, by siRNA, impairs ionizing radiation-induced intra-S-phase and G(2)/M checkpoints. Inhibition of the expression of Mcph1 decreases both protein and transcript levels of endogenous Brca1 but not exogenous Brca1. Mcph1 inhibition also decreases both endogenous and heterologous Chk1 transcripts and protein. We conclude that Mcph1 is involved in DNA damage-induced cellular responses, and we propose that regulation of Brca1 and/or Chk1 by Mcph1 may contribute to these cellular responses.

PMID:
15220350
DOI:
10.1074/jbc.C400139200
[Indexed for MEDLINE]
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