Year: 2004
Type: article
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.
Source: Journal of Biological Chemistry
Authors: Xingzhi Xu, Juhie Lee, David F. Stern
Institution: Yale University
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funder: National Cancer Institute
OpenAlex ID: W2089371078