Journal of Biological Chemistry
Volume 283, Issue 43, 24 October 2008, Pages 29586-29592
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DNA: Replication, Repair, Recombination, and Chromosome Dynamics
Microcephalin/MCPH1 Associates with the Condensin II Complex to Function in Homologous Recombination Repair

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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.

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This work was supported, in whole or in part, by National Institutes of Health Grants CA92312 and CA100109 (to J. C.) and R01CA109574-01A1 (to K. L.). This work was also supported by The Susan G. Komen Breast Cancer Foundation Grant BCTR0504162T (to K. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Recipient of a National Research Service Award F31 GM770802.