Microcephalin and pericentrin regulate mitotic entry via centrosome-associated Chk1

被引：79

作者：

Tibelius, Alexandra ^{[1
,3
]}

Marhold, Joachim ^{[1
,3
]}

Zentgraf, Hanswalter ^{[2
]}

Heilig, Christoph E. ^{[1
,3
]}

Neitzel, Heidemarie ^{[4
]}

Ducommun, Bernard ^{[5
]}

Rauch, Anita ^{[6
]}

Ho, Anthony D. ^{[3
]}

Bartek, Jiri ^{[7
,8
]}

Kraemer, Alwin ^{[1
,3
]}

机构：

[1] German Canc Res Ctr, Clin Cooperat Unit Mol Hematol Oncol, D-69120 Heidelberg, Germany

[2] German Canc Res Ctr, Dept Tumor Virol, D-69120 Heidelberg, Germany

[3] Univ Heidelberg, Dept Internal Med 5, D-69120 Heidelberg, Germany

[4] Univ Berlin, Charite, Inst Human Genet, D-14195 Berlin, Germany

[5] CNRS, Lab Biol Cellulaire & Mol Controle Proliferat, F-31062 Toulouse, France

[6] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, D-91054 Erlangen, Germany

[7] Danish Canc Soc, Inst Canc Biol, DK-2100 Copenhagen, Denmark

[8] Danish Canc Soc, Ctr Genotox Stress Res, DK-2100 Copenhagen, Denmark

来源：

JOURNAL OF CELL BIOLOGY | 2009年 / 185卷 / 07期

关键词：

SECKEL-SYNDROME; DNA-DAMAGE; CHROMOSOME CONDENSATION; BRAIN SIZE; MUTATIONS; CDC25B; CELLS; IDENTIFICATION; DEFECTS; EVENTS;

D O I：

10.1083/jcb.200810159

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Primary microcephaly, Seckel syndrome, and microcephalic osteodysplastic primordial dwarfism type II (MOPD II) are disorders exhibiting marked microcephaly, with small brain sizes reflecting reduced neuron production during fetal life. Although primary microcephaly can be caused by mutations in microcephalin (MCPH1), cells from patients with Seckel syndrome and MOPD II harbor mutations in ataxia telangiectasia and Rad3 related (ATR) or pericentrin (PCNT), leading to disturbed ATR signaling. In this study, we show that a lack of MCPH1 or PCNT results in a loss of Chk1 from centrosomes with subsequently deregulated activation of centrosomal cyclin B-Cdk1.

引用

页码：1149 / 1157

页数：9

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