Mutations in CENPE define a novel kinetochore-centromeric mechanism for microcephalic primordial dwarfism.

ABSTRACT: Defects in centrosome, centrosomal-associated and spindle-associated proteins are the most frequent cause of primary microcephaly (PM) and microcephalic primordial dwarfism (MPD) syndromes in humans. Mitotic progression and segregation defects, microtubule spindle abnormalities and impaired DNA damage-induced G2-M cell cycle checkpoint proficiency have been documented in cell lines from these patients. This suggests that impaired mitotic entry, progression and exit strongly contribute to PM and MPD. Considering the vast protein networks involved in coordinating this cell cycle stage, the list of potential target genes that could underlie novel developmental disorders is large. One such complex network, with a direct microtubule-mediated physical connection to the centrosome, is the kinetoc

SUBMITTER: Mirzaa GM 

PROVIDER: S-EPMC4415612 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature