原创力文档brit1mcph1 is essential for mitotic and meiotic recombination dna repair and maintaining genomic stability in micebrit1mcph1至关重要的有丝分裂和减数分裂重组dna修复和维持基因组稳定的老鼠.pdfVIP
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brit1mcph1 is essential for mitotic and meiotic recombination dna repair and maintaining genomic stability in micebrit1mcph1至关重要的有丝分裂和减数分裂重组dna修复和维持基因组稳定的老鼠
BRIT1/MCPH1 Is Essential for Mitotic and Meiotic
Recombination DNA Repair and Maintaining Genomic
Stability in Mice
1 1 2 2 3¤ 3 1
Yulong Liang , Hong Gao , Shiaw-Yih Lin , Guang Peng , Xingxu Huang , Pumin Zhang , John A. Goss ,
1 4 4 1
Francis C. Brunicardi , Asha S. Multani , Sandy Chang , Kaiyi Li *
1The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America, 2 Department of Systems Biology, M. D. Anderson
Cancer Center, Houston, Texas, United States of America, 3 Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States
of America, 4 Department of Molecular Genetics, M. D. Anderson Cancer Center, Houston, Texas, United States of America
Abstract
BRIT1 protein (also known as MCPH1) contains 3 BRCT domains which are conserved in BRCA1, BRCA2, and other important
molecules involved in DNA damage signaling, DNA repair, and tumor suppression. BRIT1 mutations or aberrant expression
are found in primary microcephaly patients as well as in cancer patients. Recent in vitro studies suggest that BRIT1/MCPH1
functions as a novel key regulator in the DNA damage response pathways. To investigate its physiological role and dissect
the underlying mechanisms, we generated BRIT12/ 2 mice and identified its essential roles in mitotic and meiotic
recombination DNA repair and in maintaining genomic stability. Both BRIT12/ 2 mice and mouse embryonic fibroblasts
(MEFs) were hypersensitive to c-irradiation. BRIT12/ 2 MEFs and T lymphocytes exhibited severe chromatid
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