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| Status |
Public on May 13, 2024 |
| Title |
Genome wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
DNA replication progression can be affected by the presence of physical barriers on the DNA, like RNA Polymerases, leading to replication stress and DNA damage. To characterize what happens at sites where DNA replication forks stall and pause, we establish a genome-wide approach to identify them. This approach uses multiple timepoints during S-phase, to identify replication fork/stalling hotspots throughout the genome. These sites are typically associated with increased DNA damage, overlap with fragile sites and with breakpoints of rearrangements identified in cancers, but do not overlap with replication origins. Overlaying these sites with a genome-wide analysis of RNA Polymerase II transcription, we found that replication fork stalling/pausing sites inside genes are directly related to transcription progression and activity. This would support data that indicate that transcription and replication can coexist over the same regions. We found instances where transcription activity by reducing histone density favors replication progression through genes, but also found that slowing down transcription elongation slows down directly replication progression through genes. Importantly, rearrangements found in cancers at transcription-replication collision sites can be detected in non-transformed cells and increased following treatment with ATM and ATR inhibitors. Altogether, our findings highlight how transcription and replication overlap during S-phase, with both positive and negative consequences for replication fork progression and genome stability.
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| |
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| Overall design |
Genome-wide DNA replication profile of BJ-hTERT during S phase with or without indicated treatments generated by NGS
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| |
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| Contributor(s) |
Rojas P, Wang J, Saponaro M |
| Citation(s) |
38773641 |
| |
| Submission date |
Mar 25, 2021 |
| Last update date |
Jun 06, 2024 |
| Contact name |
Marco Saponaro |
| E-mail(s) |
m.saponaro@bham.ac.uk
|
| Organization name |
University of Birmingham
|
| Department |
Institute of Cancer and Genomic Sciences
|
| Street address |
Vincent Drive
|
| City |
Birmingham |
| ZIP/Postal code |
B15 2TT |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE169620 |
Genome wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression |
|
| Relations |
| BioProject |
PRJNA717229 |
| SRA |
SRP312120 |
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