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000294321 1001_ $$0P:(DE-He78)3ffdda266b4958f6a267fa2ce18f2762$$aWagner, Rebecca$$b0$$eFirst author$$udkfz
000294321 245__ $$aSRSF2 safeguards efficient transcription of DNA damage and repair genes.
000294321 260__ $$a[New York, NY]$$bElsevier$$c2024
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000294321 520__ $$aThe serine-/arginine-rich splicing factor 2 (SRSF2) plays pivotal roles in pre-mRNA processing and gene transcription. Recurrent mutations, particularly a proline-to-histidine substitution at position 95 (P95H), are common in neoplastic diseases. Here, we assess SRSF2's diverse functions in squamous cell carcinoma. We show that SRSF2 deletion or homozygous P95H mutation both cause extensive DNA damage leading to cell-cycle arrest. Mechanistically, SRSF2 regulates efficient bi-directional transcription of DNA replication and repair genes, independent from its function in splicing. Further, SRSF2 haploinsufficiency induces DNA damage without halting the cell cycle. Exposing mouse skin to tumor-promoting carcinogens enhances the clonal expansion of heterozygous Srsf2 P95H epidermal cells but unexpectedly inhibits tumor formation. To survive carcinogen treatment, Srsf2 P95H+/- cells undergo substantial transcriptional rewiring and restore bi-directional gene expression. Thus, our study underscores SRSF2's importance in regulating transcription to orchestrate the cell cycle and the DNA damage response.
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000294321 650_7 $$2Other$$aCP: Cancer
000294321 650_7 $$2Other$$aCP: Molecular biology
000294321 650_7 $$2Other$$aDNA damage
000294321 650_7 $$2Other$$aDNA repair
000294321 650_7 $$2Other$$aDNA replication
000294321 650_7 $$2Other$$aTranscription
000294321 650_7 $$2Other$$abi-directional promoters
000294321 650_7 $$2Other$$aepithelia
000294321 650_7 $$2Other$$askin
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000294321 7001_ $$aBritto-Borges, Thiago$$b2
000294321 7001_ $$0P:(DE-He78)a3d2e48d4d32d6b3952996020fe8d1b5$$aHeit-Mondrzyk, Anke$$b3$$udkfz
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000294321 7001_ $$0P:(DE-He78)690891e88caacd9f6327522d7d167149$$aSollier, Etienne$$b5$$udkfz
000294321 7001_ $$aGkatza, Nikoletta A$$b6
000294321 7001_ $$0P:(DE-He78)d4405881b542f40197770d457d737895$$aPanten, Jasper$$b7$$udkfz
000294321 7001_ $$0P:(DE-He78)7db81e03313a2df5e17380868363a0d8$$aDelaunay, Sylvain$$b8$$udkfz
000294321 7001_ $$0P:(DE-He78)bdd027a3817257abc3d945ab048d2ab3$$aSohn, Daniela$$b9$$udkfz
000294321 7001_ $$0P:(DE-He78)141ce740f5d881812d2675147b72ecaf$$aSchmezer, Peter$$b10
000294321 7001_ $$0P:(DE-He78)4c21317940f3ec566480ebcdcff3e00c$$aOdom, Duncan T$$b11$$udkfz
000294321 7001_ $$0P:(DE-He78)799d978330dff449f8244947929a4518$$aMüller-Decker, Karin$$b12
000294321 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b13$$udkfz
000294321 7001_ $$aDieterich, Christoph$$b14
000294321 7001_ $$0P:(DE-He78)ff1677c63392be9b31a1c8d23db7c9dc$$aLutsik, Pavlo$$b15$$udkfz
000294321 7001_ $$aBornelöv, Susanne$$b16
000294321 7001_ $$0P:(DE-He78)78bbb829c94caf04ce9b6fb4a5b13edc$$aFrye, Michaela$$b17$$eLast author$$udkfz
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