RNA-mediated double-strand break repair by end-joining mechanisms

Youngkyu Jeon, Yilin Lu, Margherita Maria Ferrari, Tejasvi Channagiri, Penghao Xu, Chance Meers, Yiqi Zhang, Sathya Balachander, Vivian S. Park, Stefania Marsili, Zachary F. Pursell, Nataša Jonoska () and Francesca Storici ()
Additional contact information
Youngkyu Jeon: Georgia Institute of Technology
Yilin Lu: Georgia Institute of Technology
Margherita Maria Ferrari: University of South Florida
Tejasvi Channagiri: University of South Florida
Penghao Xu: Georgia Institute of Technology
Chance Meers: Georgia Institute of Technology
Yiqi Zhang: Georgia Institute of Technology
Sathya Balachander: Georgia Institute of Technology
Vivian S. Park: Tulane University of Medicine
Stefania Marsili: Georgia Institute of Technology
Zachary F. Pursell: Tulane University of Medicine
Nataša Jonoska: University of South Florida
Francesca Storici: Georgia Institute of Technology

Nature Communications, 2024, vol. 15, issue 1, 1-24

Abstract: Abstract Double-strand breaks (DSBs) in DNA are challenging to repair. Cells employ at least three DSB-repair mechanisms, with a preference for non-homologous end joining (NHEJ) over homologous recombination (HR) and microhomology-mediated end joining (MMEJ). While most eukaryotic DNA is transcribed into RNA, providing complementary genetic information, much remains unknown about the direct impact of RNA on DSB-repair outcomes and its role in DSB-repair via end joining. Here, we show that both sense and antisense-transcript RNAs impact DSB repair in a sequence-specific manner in wild-type human and yeast cells. Depending on its sequence complementarity with the broken DNA ends, a transcript RNA can promote repair of a DSB or a double-strand gap in its DNA gene via NHEJ or MMEJ, independently from DNA synthesis. The results demonstrate a role of transcript RNA in directing the way DSBs are repaired in DNA, suggesting that RNA may directly modulate genome stability and evolution.

Date: 2024
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DOI: 10.1038/s41467-024-51457-9

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