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000289903 1001_ $$0P:(DE-He78)aba46ac1c64436abf1d83601635be98e$$aCorazzi, Lorenzo$$b0$$eFirst author$$udkfz
000289903 245__ $$aLinear interaction between replication and transcription shapes DNA break dynamics at recurrent DNA break Clusters.
000289903 260__ $$a[London]$$bNature Publishing Group UK$$c2024
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000289903 520__ $$aRecurrent DNA break clusters (RDCs) are replication-transcription collision hotspots; many are unique to neural progenitor cells. Through high-resolution replication sequencing and a capture-ligation assay in mouse neural progenitor cells experiencing replication stress, we unravel the replication features dictating RDC location and orientation. Most RDCs occur at the replication forks traversing timing transition regions (TTRs), where sparse replication origins connect unidirectional forks. Leftward-moving forks generate telomere-connected DNA double-strand breaks (DSBs), while rightward-moving forks lead to centromere-connected DSBs. Strand-specific mapping for DNA-bound RNA reveals co-transcriptional dual-strand DNA:RNA hybrids present at a higher density in RDC than in other actively transcribed long genes. In addition, mapping RNA polymerase activity uncovers that head-to-head interactions between replication and transcription machinery result in 60% DSB contribution to the head-on compared to 40% for co-directional. Taken together we reveal TTR as a fragile class and show how the linear interaction between transcription and replication impacts genome stability.
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000289903 650_7 $$09007-49-2$$2NLM Chemicals$$aDNA
000289903 650_2 $$2MeSH$$aAnimals
000289903 650_2 $$2MeSH$$aTranscription, Genetic
000289903 650_2 $$2MeSH$$aDNA Breaks, Double-Stranded
000289903 650_2 $$2MeSH$$aMice
000289903 650_2 $$2MeSH$$aDNA Replication
000289903 650_2 $$2MeSH$$aGenomic Instability
000289903 650_2 $$2MeSH$$aNeural Stem Cells: metabolism
000289903 650_2 $$2MeSH$$aDNA: metabolism
000289903 650_2 $$2MeSH$$aDNA: genetics
000289903 650_2 $$2MeSH$$aReplication Origin
000289903 650_2 $$2MeSH$$aTelomere: metabolism
000289903 650_2 $$2MeSH$$aTelomere: genetics
000289903 650_2 $$2MeSH$$aCentromere: metabolism
000289903 650_2 $$2MeSH$$aCentromere: genetics
000289903 7001_ $$0P:(DE-He78)3aee16150bf35687a9dbf97322ac800b$$aIonasz, Vivien$$b1$$eFirst author$$udkfz
000289903 7001_ $$0P:(DE-He78)0f0276d7e9af07e98339a060db121ab2$$aAndrejev, Sergej$$b2
000289903 7001_ $$0P:(DE-He78)829b0f546af90cfbecb8041bd2c90272$$aWang, Li-Chin$$b3$$udkfz
000289903 7001_ $$aVouzas, Athanasios$$b4
000289903 7001_ $$0P:(DE-He78)efc78b368f4fab8939f838a4d1318e87$$aGiaisi, Marco$$b5$$udkfz
000289903 7001_ $$0P:(DE-He78)a589383be16687889678202ce8552a55$$aDi Muzio, Giulia$$b6$$udkfz
000289903 7001_ $$0P:(DE-He78)3409e567689d5b9d879d0aeab03ed78d$$aDing, Boyu$$b7$$udkfz
000289903 7001_ $$0P:(DE-He78)30ad7f8eab7a3307853f27691589f239$$aMarx, Anna$$b8$$udkfz
000289903 7001_ $$0P:(DE-He78)8dd69d7a6c9e29cb655f698dc7378788$$aHenkenjohann, Jonas$$b9$$udkfz
000289903 7001_ $$0P:(DE-He78)b604fd807e924ba9f08183d54bb15b9e$$aAllers, Michael$$b10$$udkfz
000289903 7001_ $$00000-0001-8087-9737$$aGilbert, David M$$b11
000289903 7001_ $$0P:(DE-He78)56a961d57d7839fc2d2ebb60c575d9c4$$aWei, Pei-Chi$$b12$$eLast author$$udkfz
000289903 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-024-47934-w$$gVol. 15, no. 1, p. 3594$$n1$$p3594$$tNature Communications$$v15$$x2041-1723$$y2024
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