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Loss of the tumour-suppressor genes CHK2 and BRCA1 results in chromosomal instability

尼德兰添加于 2010-12-4 16:11 | 1866 次阅读 | 0 个评论

作者
Stolz A, Ertych N, Bastians H
摘要
CHK2 (checkpoint kinase 2) and BRCA1 (breast cancer early-onset 1) are tumour-suppressor genes that have been implicated previously in the DNA damage response. Recently, we have identified CHK2 and BRCA1 as genes required for the maintenance of chromosomal stability and have shown that a Chk2-mediated phosphorylation of Brca1 is required for the proper and timely assembly of mitotic spindles. Loss of CHK2, BRCA1 or inhibition of its Chk2-mediated phosphorylation inevitably results in the transient formation of abnormal spindles that facilitate the establishment of faulty microtubule-kinetochore attachments associated with the generation of lagging chromosomes. Importantly, both CHK2 and BRCA1 are lost at very high frequency in aneuploid lung adenocarcinomas that are typically induced in knockout mice exhibiting chromosomal instability. Thus these results suggest novel roles for Chk2 and Brca1 in mitosis that might contribute to their tumour-suppressor functions.
详细资料
- 文献种类:期刊
- 期刊名称: Biochemical Society Transactions
- 期刊缩写: Biochem Soc Trans
- 期卷页: 2010年第38卷第6期 1704-1708页
- 地址: Philipps University Marburg, Institute of Molecular Biology and Tumor Research (IMT), Emil-Mannkopff-Strasse 2, D-35037 Marburg, Germany
- ISBN: 0300-5127
- 备注:PMID:21118151
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