Home > Publications database > Linear interaction between replication and transcription shapes DNA break dynamics at recurrent DNA break Clusters. > print

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005     20250328112418.0
024 7 _ |a 10.1038/s41467-024-47934-w
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100 1 _ |a Corazzi, Lorenzo
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245 _ _ |a Linear interaction between replication and transcription shapes DNA break dynamics at recurrent DNA break Clusters.
260 _ _ |a [London]
|c 2024
|b Nature Publishing Group UK
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520 _ _ |a Recurrent 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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650 _ 7 |a DNA
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650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Transcription, Genetic
|2 MeSH
650 _ 2 |a DNA Breaks, Double-Stranded
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a DNA Replication
|2 MeSH
650 _ 2 |a Genomic Instability
|2 MeSH
650 _ 2 |a Neural Stem Cells: metabolism
|2 MeSH
650 _ 2 |a DNA: metabolism
|2 MeSH
650 _ 2 |a DNA: genetics
|2 MeSH
650 _ 2 |a Replication Origin
|2 MeSH
650 _ 2 |a Telomere: metabolism
|2 MeSH
650 _ 2 |a Telomere: genetics
|2 MeSH
650 _ 2 |a Centromere: metabolism
|2 MeSH
650 _ 2 |a Centromere: genetics
|2 MeSH
700 1 _ |a Ionasz, Vivien
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700 1 _ |a Andrejev, Sergej
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700 1 _ |a Wang, Li-Chin
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700 1 _ |a Vouzas, Athanasios
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700 1 _ |a Giaisi, Marco
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700 1 _ |a Di Muzio, Giulia
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700 1 _ |a Ding, Boyu
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700 1 _ |a Marx, Anna
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700 1 _ |a Henkenjohann, Jonas
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700 1 _ |a Allers, Michael
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700 1 _ |a Gilbert, David M
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700 1 _ |a Wei, Pei-Chi
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773 _ _ |a 10.1038/s41467-024-47934-w
|g Vol. 15, no. 1, p. 3594
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856 4 _ |u https://inrepo02.dkfz.de/record/289903/files/s41467-024-47934-w.pdf
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