The role of MCPH1, a protein responsible for primary microcephaly, in chromosome condensation

人类MCPH1(HMCPH1)的突变会导致原发性小头畸形，其特征是大脑明显缩小。HMCPH1突变患者细胞在G2期表现出独特的细胞表型，包括染色体过早凝聚(PCC)。为了研究MCPH1在染色体凝聚中的作用，我开发了一种使用非洲爪哇卵子提取物的无细胞检测方法。结果表明，hMCPH1的N-末端结构域在体外特异性地抑制了凝聚素II的作用。用患者细胞进行的互补分析表明，hMCPH1的N-末端结构域足以挽救PCC表型。因此，hMCPH1作为凝聚素II的直接调节器来调节染色体凝聚。

Mutations in human MCPH1(hMCPH1) cause primary microcephaly, which is characterized by a marked reduction of brain size. hMCPH1 mutant patient cells display unique cellular phenotypes, including premature chromosome condensation(PCC), in G2 phase. To examine a role of MCPH1 in chromosome condensation, I developed a cell-free assay using Xenopus egg extracts. The results demonstrated that an N-terminal domain of hMCPH1 specifically inhibits the action of condensin II in vitro. A complementation assay using patient cells revealed that the N-terminal domain of hMCPH1 is sufficient to rescue the PCC phenotype. Thus, hMCPH1 acts as a direct modulator of condensin II to regulate chromosome condensation.