RNA-mediated Double-strand Break Repair by End-joining Mechanisms

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Sep 11

PMID 39261460

Authors

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

Natasa Jonoska

Francesca Storici

Affiliations

Soon will be listed here.

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.

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