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Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells
Xu X.3; Weaver Z.2; Linke S.P.1; Li C.3; Gotay J.3; Wang X.-W.1; Harris C.C.1; Ried T.2; Deng C.-X.3
1999
Source PublicationMolecular Cell
ISSN10972765
Volume3Issue:3Pages:389-395
Abstract

Germline mutations of the Brca1 tumor suppressor gene predispose women to breast and ovarian cancers. To study mechanisms underlying BRCA1-related tumorigenesis, we derived mouse embryonic fibroblast cells carrying a targeted deletion of exon 11 of the Brca1 gene. We show that the mutant cells maintain an intact G-S cell cycle checkpoint and proliferate poorly. However, a defective G-M checkpoint in these cells is accompanied by extensive chromosomal abnormalities. Mutant fibroblasts contain multiple, functional centrosomes, which lead to unequal chromosome segregation, abnormal nuclear division, and aneuploidy. These data uncover an essential role of BRCA1 in maintaining genetic stability through the regulation of centrosome duplication and the G-M checkpoint and provide a molecular basis for the role of BRCA1 in tumorigenesis.

DOI10.1016/S1097-2765(00)80466-9
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000079459300013
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Cited Times [WOS]:646   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorDeng C.-X.
Affiliation1.National Cancer Institute
2.National Human Genome Research Institute
3.National Institute of Diabetes and Digestive and Kidney Diseases
Recommended Citation
GB/T 7714
Xu X.,Weaver Z.,Linke S.P.,et al. Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells[J]. Molecular Cell,1999,3(3):389-395.
APA Xu X..,Weaver Z..,Linke S.P..,Li C..,Gotay J..,...&Deng C.-X..(1999).Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells.Molecular Cell,3(3),389-395.
MLA Xu X.,et al."Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells".Molecular Cell 3.3(1999):389-395.
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