Formin-mediated epigenetic maintenance of centromere identity

Accurate chromosome segregation in mammalian cells is guided by the centromere, a specialized chromosome region defined by the histone H3 variant centromere protein A (CENP-A). It is not well understood how cells maintain CENP-A levels at centromeres while continuously going through genome replications and cell divisions. A MgcRacGAP-dependent small GTPase molecular switch has been shown as essential for centromeric CENP-A maintenance. By using quantitative imaging, pulse-chase and live cell analysis, a recent work has suggested that the diaphanous formin mDia2, a well-established small GTPase effector, functions downstream of this small GTPase pathway to maintain CENP-A levels at centromeres. A constitutively active mDia2 construct is able to rescue the CENP-A loading defect caused by MgcRacGAP depletion. This study has uncovered an unsuspected role of the cytoskeleton protein mDia2 as an effector of the MgcRacGAP-dependent small GTPase signaling inside the nucleus to participate in the epigenetic regulation of centromere maintenance during cell cycle.