Werner syndrome protein prevents DNA breaks upon chromatin structure alteration.
Werner syndrome protein prevents DNA breaks upon chromatin structure alteration.
复制标题
沃纳综合征蛋白可防止染色质结构改变时 DNA 断裂。
DOI：
10.1111/j.1474-9726.2007.00301.x
复制
发表时间：
2007
期刊：
影响因子：
7.8
通讯作者：
Lebel,Michel
中科院分区：
文献类型：
--
作者：
Turaga,RamachanderVN;Massip,Laurent;Chavez,Alejandro;Johnson,FBrad;Lebel,Michel
Werner syndrome is a rare disorder characterized by genome instability and the premature onset of several pathologies associated with aging. The gene responsible for Werner syndrome codes for a RecQ‐type DNA helicase and is believed to be involved in different aspects of DNA repair, replication, and transcription. The human Werner protein (WRN) translocates from nucleoli to the nucleoplasm upon DNA damage. Here, for the first time we show WRN translocation following treatment with chloroquine (CHL) or trichostatin A (TSA), agents that alter chromatin structure without producing DNA breaks. In contrast to normal cells, WRN deficient human and murine cells incurred extensive DNA breaks upon CHL or TSA treatment, indicating a functional role for WRN in the proper response to these agents. Cells deficient for another RecQ‐type helicase, Bloom syndrome, were not sensitive to these agents. WRN is known fromin vitrostudies to bind and stimulate the activity of topoisomerase I (TopoI). CHL enhanced the association between WRN and TopoI, suggesting that topological stress elicits a requirement for the stimulation of TopoI by WRN. Supporting this idea, overexpression of TopoI reduced CHL and TSA‐induced DNA breaks in WRN null cells. We thus describe a novel function for WRN in ensuring genome stability to act in concert with TopoI to prevent DNA breaks, following alterations in chromatin topology.
