文章基本信息

标题：Unrepaired clustered DNA lesions induce chromosome breakage in human cells
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作者：Aroumougame Asaithamby ; Burong Hu ; David J. Chen 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2011
卷号：108
期号：20
页码：8293-8298
DOI：10.1073/pnas.1016045108
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Clustered DNA damage induced by ionizing radiation is refractory to repair and may trigger carcinogenic events for reasons that are not well understood. Here, we used an in situ method to directly monitor induction and repair of clustered DNA lesions in individual cells. We showed, consistent with biophysical modeling, that the kinetics of loss of clustered DNA lesions was substantially compromised in human fibroblasts. The unique spatial distribution of different types of DNA lesions within the clustered damages, but not the physical location of these damages within the subnuclear domains, determined the cellular ability to repair the damage. We then examined checkpoint arrest mechanisms and yield of gross chromosomal aberrations. Induction of nonrepairable clustered damage affected only G2 accumulation but not the early G2/M checkpoint. Further, cells that were released from the G2/M checkpoint with unrepaired clustered damage manifested a spectrum of chromosome aberrations in mitosis. Difficulties associated with clustered DNA damage repair and checkpoint release before the completion of clustered DNA damage repair appear to promote genome instability that may lead to carcinogenesis.
关键词：heterochromatin ; high linear energy transfer ; high charge and energy particles ; 53BP1 ; ionizing radiation induced foci