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| Status |
Public on Jul 11, 2024 |
| Title |
RAD52 resolves replication-transcription collisions to mitigate R-loop induced genome instability |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Collisions of transcription and replication machinery on the same DNA strand can pose a significant threat to genomic stability. These collision occur in part due to of RNA-DNA hybrids termed R-loops, in which a newly synthesized RNA molecule hybridizes with the DNA template strand. This study investigated the novel role of RAD52, a known DNA repair factor, in preventing collisions by managing R-loop formation and resolution. We show that RAD52 deficiency increases R-loop accumulation, exacerbating collisions and resulting in elevated DNA damage. Further, RAD52's ability to interact with the transcription machinery, coupled with its capacity to facilitate R-loop dissolution, highlights its role in preventing collisions. Lastly, we provide the first evidence of an increased mutational burden at conserved R-loop sites in human tumor samples. In summary, this study underscores the importance of RAD52 in orchestrating the delicate balance between replication and transcription processes to prevent collisions and maintain genome stability.
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| Overall design |
In HeLa cells: ChIP-seq of RNA Pol II (Rpb1), gH2AX and S9.6 in untreated (siNT) andd RAD52-depleted (si52) cells; ChIP-seq of RAD52 in untreated (siNT) cells.
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| |
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| Contributor(s) |
Powell SN |
| Citation(s) |
39237529 |
| BioProject |
PRJNA1056281 |
| |
| Submission date |
May 02, 2024 |
| Last update date |
Oct 08, 2024 |
| Contact name |
Nils Weinhold |
| E-mail(s) |
weinholn@mskcc.org
|
| Organization name |
Memorial Sloan Kettering Cancer Center
|
| Street address |
1275 York Avenue
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
|
| GSM8247992 |
siNT_S96_1.mkD.clN.sorted.bam.ratio.CPM.bw |
| GSM8247993 |
siNT_Rpb1_1.mkD.clN.sorted.bam.ratio.CPM.bw |
| GSM8247994 |
siNT_Rad52_1.mkD.clN.sorted.bam.ratio.CPM.bw |
| GSM8247995 |
siNT_gH2Ax_1.mkD.clN.sorted.bam.ratio.CPM.bw |
| GSM8247996 |
si52_S96_1.mkD.clN.sorted.bam.ratio.CPM.bw |
| GSM8247997 |
si52_Rpb1_1.mkD.clN.sorted.bam.ratio.CPM.bw |
| GSM8247998 |
si52_gH2Ax_1.mkD.clN.sorted.bam.ratio.CPM.bw |
| GSM8247999 |
input_1.mkD.clN.sorted.bam.ratio.CPM.bw |
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