RAD52 resolves transcription-replication conflicts to mitigate R-loop induced genome instability

Manisha Jalan (), Aman Sharma, Xin Pei, Nils Weinhold, Erika S. Buechelmaier, Yingjie Zhu, Sana Ahmed-Seghir, Abhirami Ratnakumar, Melody Bona, Niamh McDermott, Joan Gomez-Aguilar, Kyrie S. Anderson, Charlotte K. Y. Ng, Pier Selenica, Samuel F. Bakhoum, Jorge S. Reis-Filho, Nadeem Riaz and Simon N. Powell ()
Additional contact information
Manisha Jalan: MSKCC
Aman Sharma: MSKCC
Xin Pei: MSKCC
Nils Weinhold: MSKCC
Erika S. Buechelmaier: MSKCC
Yingjie Zhu: MSKCC
Sana Ahmed-Seghir: MSKCC
Abhirami Ratnakumar: MSKCC
Melody Bona: MSKCC
Niamh McDermott: MSKCC
Joan Gomez-Aguilar: MSKCC
Kyrie S. Anderson: MSKCC
Charlotte K. Y. Ng: University of Bern
Pier Selenica: MSKCC
Samuel F. Bakhoum: MSKCC
Jorge S. Reis-Filho: MSKCC
Nadeem Riaz: MSKCC
Simon N. Powell: MSKCC

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-51784-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51784-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-51784-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().