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• W2076127482 abstract "WRN is a member of the RecQ family of DNA helicases implicated in the resolution of DNA structures leading to the stall of replication forks. Fragile sites have been proposed to be DNA regions particularly sensitive to replicative stress. Here, we establish that WRN is a key regulator of fragile site stability. We demonstrate that in response to mild doses of aphidicolin, WRN is efficiently relocalized in nuclear foci in replicating cells and that WRN deficiency is associated with accumulation of gaps and breaks at common fragile sites even under unperturbed conditions. By expressing WRN isoforms impaired in either helicase or exonuclease activity in defective cells, we identified WRN helicase activity as the function required for maintaining the stability of fragile sites. Finally, we find that WRN stabilizes fragile sites acting in a common pathway with the ataxia telangiectasia and Rad3 related replication checkpoint. These findings provide the first evidence of a crucial role for a helicase in protecting cells against chromosome breakage at normally occurring replication fork stalling sites." @default.
• W2076127482 created "2016-06-24" @default.
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• W2076127482 date "2008-01-21" @default.
• W2076127482 modified "2023-09-27" @default.
• W2076127482 title "Werner syndrome helicase activity is essential in maintaining fragile site stability" @default.
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• W2076127482 doi "https://doi.org/10.1083/jcb.200705126" @default.
• W2076127482 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2213598" @default.
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