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• W1971776319 abstract "Transcription is a major obstacle for replication fork (RF) progression and a cause of genome instability. Part of this instability is mediated by cotranscriptional R loops, which are believed to increase by suboptimal assembly of the nascent messenger ribonucleoprotein particle (mRNP). However, no clear evidence exists that heterogeneous nuclear RNPs (hnRNPs), the basic mRNP components, prevent R-loop stabilization. Here we show that yeast Npl3, the most abundant RNA-binding hnRNP, prevents R-loop-mediated genome instability. npl3Δ cells show transcription-dependent and R-loop-dependent hyperrecombination and genome-wide replication obstacles as determined by accumulation of the Rrm3 helicase. Such obstacles preferentially occur at long and highly expressed genes, to which Npl3 is preferentially bound in wild-type cells, and are reduced by RNase H1 overexpression. The resulting replication stress confers hypersensitivity to double-strand break-inducing agents. Therefore, our work demonstrates that mRNP factors are critical for genome integrity and opens the option of using them as therapeutic targets in anti-cancer treatment." @default.
• W1971776319 created "2016-06-24" @default.
• W1971776319 creator A5043281613 @default.
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• W1971776319 date "2013-11-15" @default.
• W1971776319 modified "2023-10-02" @default.
• W1971776319 title "The Npl3 hnRNP prevents R-loop-mediated transcription–replication conflicts and genome instability" @default.
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• W1971776319 doi "https://doi.org/10.1101/gad.229880.113" @default.
• W1971776319 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3841734" @default.
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