Microcephalin/MCPH1 Associates with the Condensin II Complex to Function in Homologous Recombination Repair

Dual recognition of phosphoserine and phosphotyrosine in histone variant H2A.X by DNA damage response protein MCPH1

“…Thus, whereas the BRCT domains of MCPH1 and MDC1 are direct readers of γH2A.X, this ability may be harnessed as part of larger DNA damage sensing multiprotein assemblies to gain access to sites of DSBs. Such is likely the case for MCPH1, an established component of the BRCA2/ Rad51 (33), SWI/SNF (15), and Condensin II (34,35) complexes that need to be directed to damaged sites. Future work is required to decipher the amounts of MCPH1 parsed into each of these and other complexes and the contribution of MCPH1-γH2A.X interaction toward their targeting.…”

“…The protein Microcephalin or MCPH1 is a case in point. MCPH1 is implicated in chromatin remodeling by virtue of its interaction with the SWI/SNF complex (15), in signaling programs via its association with Chk1 among other proteins (11,(29)(30)(31)(32), and aids the DNA repair process by interacting with BRCA2 (33) and Condensin II (34,35). Because of its involvement in multiple processes that converge to maintain genomic integrity, MCPH1 has been termed a "guardian of the genome" (13).…”

MCPH1/BRIT1 limits ionizing radiation-induced centrosome amplification

“…MCPH1 RNA interference in lymphoblastoid cells had no effect on the mitotic index (Alderton et al, 2006). Chromosome condensation defects have been observed in two murine models of Mcph1 deficiency, but detailed mitotic analysis has not yet been reported (Wood et al, 2008;Liang et al, 2010;Trimborn et al, 2010). Analysis of Drosophila Mcph1 mutants revealed syncytial embryonic lethality that is associated with mitotic arrest, but no such impact was seen in adult flies (Brunk et al, 2007;Rickmyre et al, 2007).…”

“…MCPH1 knockdown cells and Mcph1 À/À mice and cells also show increased radiosensitivity (Peng et al, 2009;Liang et al, 2010). Defective homologous recombination and a chromosome condensation defect have been observed in Mcph1 À/À mouse cells (Wood et al, 2008;Liang et al, 2010;Trimborn et al, 2010) and a role for MCPH1 in controlling homologous recombination activities has been described in human cells (Peng et al, 2009;Wu et al, 2009). A recent paper has shown that MCPH1 regulates the adenosine triphosphate-dependent chromatin remodelling of SWI-SNF complex, altering the chromatin structure in response to DNA damage to facilitate DNA repair (Peng et al, 2009).…”

The Centrosome and Its Duplication Cycle

“…MCPH1 appears in radiation-induced nuclear foci (Rai et al 2006) and specifically regulates levels of both BRCA1 and Chk1 (Xu et al 2004;Lin et al 2005;Tibelius et al 2009). MCPH1 knockdown cells show increased radiosensitivity (Peng et al 2009;Liang et al 2010) as well as recombination and chromosome condensation defects (Wood et al 2008, Liang et al 2010Trimborn et al 2010). MCPH1 also participates in altering the chromatin structure in response to DNA damage to allow DNA repair (Peng et al 2009).…”