Microcephalin/MCPH1 associates with the Condensin II complex to function in homologous recombination repair.
Microcephalin/MCPH1 is one of the causative genes responsible for the autosomal recessive disorder primary microcephaly. Patients with this disease present with mental retardation and dramatic reduction in head size, and cells derived from these patients contain abnormally condensed chromosomes. MCPH1 contains an N-terminal BRCT and tandem C-terminal BRCT domains. More recently, MCPH1 has been implicated in the cellular response to DNA damage; however, the exact mechanism remains unclear. Here, we report the identification Condensin II as a major MCPH1-interacting protein. MCPH1 and Condensin II interact in vivo, mediated by the CAPG2 subunit of Condensin II binding to a middle domain (residues 376-485) of MCPH1. Interestingly, while Condensin II is not required for the IR-induced G2/M checkpoint, Condensin II-depleted cells have a defect in HR repair, which is also present in MCPH1(-/-)MEFs. Moreover, the Condensin II binding region of MCPH1 is also required for HR function. Collectively, we have identified a novel function of MCPH1 to modulate HR repair through Condensin II, and thereby maintain genome integrity.
Wood
Jamie L
JL
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06473, USA.
Liang
Yulong
Y
Li
Kaiyi
K
Chen
Junjie
J
D000251:Adenosine Triphosphatases / Q000737:chemistry; D000595:Amino Acid Sequence; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002460:Cell Line; D003598:Cytoskeletal Proteins; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry; D016678:Genome; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C460645:MCPH1 protein, human; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C108312:condensin complexes; D000251:Adenosine Triphosphatases