RAD52 resolves transcription-replication conflicts to mitigate R-loop induced genome instability Journal Article
| Authors: | Jalan, M.; Sharma, A.; Pei, X.; Weinhold, N.; Buechelmaier, E. S.; Zhu, Y.; Ahmed-Seghir, S.; Ratnakumar, A.; Di Bona, M.; McDermott, N.; Gomez-Aguilar, J.; Anderson, K. S.; Ng, C. K. Y.; Selenica, P.; Bakhoum, S. F.; Reis-Filho, J. S.; Riaz, N.; Powell, S. N. |
| Article Title: | RAD52 resolves transcription-replication conflicts to mitigate R-loop induced genome instability |
| Abstract: | Collisions of the transcription and replication machineries on the same DNA strand can pose a significant threat to genomic stability. These collisions occur in part due to the formation of RNA-DNA hybrids termed R-loops, in which a newly transcribed RNA molecule hybridizes with the DNA template strand. This study investigated the role of RAD52, a known DNA repair factor, in preventing collisions by directing R-loop formation and resolution. We show that RAD52 deficiency increases R-loop accumulation, exacerbating collisions and resulting in elevated DNA damage. Furthermore, 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 evidence of an increased mutational burden from double-strand breaks at conserved R-loop sites in human tumor samples, which is increased in tumors with low RAD52 expression. In summary, this study underscores the importance of RAD52 in orchestrating the balance between replication and transcription processes to prevent collisions and maintain genome stability. © The Author(s) 2024. |
| Keywords: | controlled study; human cell; single nucleotide polymorphism; somatic mutation; genetics; mutation; flow cytometry; dna replication; genetic analysis; neoplasm; neoplasms; mass spectrometry; metabolism; dna damage; cell cycle; dna repair; gene expression; carboxy terminal sequence; protein protein interaction; genetic transcription; transcription, genetic; rna; dna; genomic instability; western blotting; immunoprecipitation; dna breaks, double-stranded; double stranded dna break; genome; okazaki fragment; tumor; image processing; nuclear localization signal; histone h2ax; rna polymerase ii; gene replication; single strand annealing; rad52 protein; rad52 dna repair and recombination protein; gene ontology; vinculin; humans; human; female; article; hela cell line; coimmunoprecipitation; hek293t cell line; hct 116 cell line; u2os cell line; r-loop structure; r-loop structures; rad52 protein, human |
| Journal Title: | Nature Communications |
| Volume: | 15 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-09-05 |
| Start Page: | 7776 |
| Language: | English |
| DOI: | 10.1038/s41467-024-51784-x |
| PUBMED: | 39237529 |
| PROVIDER: | scopus |
| PMCID: | PMC11377823 |
| DOI/URL: | |
| Notes: | PDF misspells MSK author: Sana Ahmed-Seghir's first name -- Source: Scopus |
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