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| Status |
Public on May 13, 2024 |
| Title |
Genomewide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
DNA replication progression can be affected by the presence of physical barriers on the DNA, like the RNA Polymerases, leading to replication stress and DNA damage. Nonetheless, we do not know the overall influence of transcription on DNA replication progression. 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 to identify replication fork/stalling hotspots as the replication progresses through 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 find that replication fork stalling/pausing sites inside genes are directly related to transcription progression and activity. We also find instances where transcription activity favors replication progression because reduces histone density, but also that slowing down transcription elongation slows down directly replication progression through genes. This would indicate that transcription and replication can coexist over the same regions. Importantly, rearrangements found in cancers overlapping transcription-replication collision sites are detected in non-transformed cells and increase 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 by the coexistence of these two processes.
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| Overall design |
Genome-wide profiles of RNAPII and PCNA in synchronous BJ-hTERT cells and generated by NEXT-seq in one biological repeats
Please note that the metagene profiles ('all_peaks.txt') are also peaks identified in the following BrdU-Seq samples (in GSE136288/PRJNA561836):
GEO Sample accns SRA experiment accns Biosample accns
GSM4044019 SRX6756306 SAMN12629357
GSM4044020 SRX6756307 SAMN12629356
GSM4044021 SRX6756308 SAMN12629355
GSM4044022 SRX6756309 SAMN12629354
GSM4044023 SRX6756310 SAMN12629353
GSM4044024 SRX6756311 SAMN12629352
GSM4044025 SRX6756312 SAMN12629351
GSM4044026 SRX6756313 SAMN12629350
GSM4044027 SRX6756314 SAMN12629349
GSM4044028 SRX6756315 SAMN12629348
GSM4044029 SRX6756316 SAMN12629347
GSM4044030 SRX6756317 SAMN12629346
BrdU peaks identified in each timepoint were all collected together in the file all_peals.txt
More specifically, BrdU peaks were called in:
GSM4044020(BrdU-Seq 16h 1) vs GSM4044019 (BrdU-Seq Input 1)
GSM4044021(BrdU-Seq 19h 1) vs GSM4044019 (BrdU-Seq Input 1)
GSM4044022(BrdU-Seq 22h 1) vs GSM4044019 (BrdU-Seq Input 1)
GSM4044023(BrdU-Seq 24h 1) vs GSM4044019 (BrdU-Seq Input 1)
GSM4044024(BrdU-Seq 28h 1) vs GSM4044019 (BrdU-Seq Input 1)
GSM4044026(BrdU-Seq 16h 2) vs GSM4044025 (BrdU-Seq Input 2)
GSM4044027(BrdU-Seq 19h 2) vs GSM4044025 (BrdU-Seq Input 2)
GSM4044028(BrdU-Seq 22h 2) vs GSM4044025 (BrdU-Seq Input 2)
GSM4044029(BrdU-Seq 24h 2) vs GSM4044025 (BrdU-Seq Input 2)
GSM4044030(BrdU-Seq 28h 2) vs GSM4044025 (BrdU-Seq Input 2)
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| Contributor(s) |
Wang J, Rojas P, Saponaro M |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
May 08, 2024 |
| Last update date |
May 13, 2024 |
| Contact name |
Marco Saponaro |
| E-mail(s) |
m.saponaro@bham.ac.uk
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| Organization name |
University of Birmingham
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| Department |
Institute of Cancer and Genomic Sciences
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| Street address |
Vincent Drive
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| City |
Birmingham |
| ZIP/Postal code |
B15 2TT |
| Country |
United Kingdom |
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| Platforms (1) |
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| Samples (4)
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| Relations |
| Reanalysis of |
GSM4044019 |
| Reanalysis of |
GSM4044020 |
| Reanalysis of |
GSM4044021 |
| Reanalysis of |
GSM4044022 |
| Reanalysis of |
GSM4044023 |
| Reanalysis of |
GSM4044024 |
| Reanalysis of |
GSM4044025 |
| Reanalysis of |
GSM4044026 |
| Reanalysis of |
GSM4044027 |
| Reanalysis of |
GSM4044028 |
| Reanalysis of |
GSM4044029 |
| Reanalysis of |
GSM4044030 |
| BioProject |
PRJNA1109387 |
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