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@ARTICLE{Corazzi:289903,
author = {L. Corazzi$^*$ and V. Ionasz$^*$ and S. Andrejev$^*$ and
L.-C. Wang$^*$ and A. Vouzas and M. Giaisi$^*$ and G. Di
Muzio$^*$ and B. Ding$^*$ and A. Marx$^*$ and J.
Henkenjohann$^*$ and M. Allers$^*$ and D. M. Gilbert and
P.-C. Wei$^*$},
title = {{L}inear interaction between replication and transcription
shapes {DNA} break dynamics at recurrent {DNA} break
{C}lusters.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2024-00895},
pages = {3594},
year = {2024},
abstract = {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.},
keywords = {Animals / Transcription, Genetic / DNA Breaks,
Double-Stranded / Mice / DNA Replication / Genomic
Instability / Neural Stem Cells: metabolism / DNA:
metabolism / DNA: genetics / Replication Origin / Telomere:
metabolism / Telomere: genetics / Centromere: metabolism /
Centromere: genetics / DNA (NLM Chemicals)},
cin = {B400},
ddc = {500},
cid = {I:(DE-He78)B400-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38678011},
doi = {10.1038/s41467-024-47934-w},
url = {https://inrepo02.dkfz.de/record/289903},
}