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

MCPH1（一种导致原发性小头畸形的蛋白质）在染色体浓缩中的作用

• 批准号: 21770196
• 负责人: YAMASHITA Daisuke
• 金额: $ 2.91万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21770196/
• 关键词: MCPH1; 染色体凝縮; コンデンシン; 小頭症; カエル卵抽出液; 進化; コンデンシンII

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.

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。

项目成果

MCPH1 patient cells exhibit delayed release from DNA damage-induced G2/M checkpoint arrest

• DOI: 10.4161/cc.9.24.14157
• 发表时间: 2010-12-15
• 期刊: CELL CYCLE
• 影响因子: 4.3
• 作者: Gavvovidis, Ioannis;Poehlmann, Charlotte;Trimborn, Marc
• 通讯作者: Trimborn, Marc

MCPH1 regulates chromosome condensation and shaping as a composite modulator of condensin II.

• DOI: 10.1083/jcb.201106141
• 发表时间: 2011-09-19
• 期刊: The Journal of cell biology
• 作者: Yamashita D;Shintomi K;Ono T;Gavvovidis I;Schindler D;Neitzel H;Trimborn M;Hirano T
• 通讯作者: Hirano T

小頭症の原因タンパク質MCPH1によるコンデンシンIIの制御

引起小头畸形的蛋白 MCPH1 对凝缩蛋白 II 的调节

• 发表时间: 2012
• 作者: 山下大輔;新冨圭史;小野教夫;Gavvovidis I.;Schindler D.;Neitzel H.;Trimborn M.;平野達也
• 通讯作者: 平野達也