A role for RNA and DNA:RNA hybrids in the modulation of DNA repair by homologous recombination

Giuseppina D'Alessandro, Marek Adamowicz, Donna Whelan, Sean Michael Howard, Corey Winston Jones-Weinert, Valentina Matti, Eli Rothenberg, Petr Cejka, Fabrizio d'Adda di Fagagna

Preprint posted on 29 January 2018

RNA in unexpected places: dilncRNAs at resected DSB ends facilitate homologous recombination-mediated repair of broken DNA

Selected by Carmen Adriaens


RNA in unexpected places: dilncRNAs at resected DSB ends facilitate homologous recombination-mediated repair of broken DNA.


The idea: 

Upon double stranded DNA break (DSB) formation, non-coding RNAs at the resected ends of the break enhance BRCA1 recruitment and facilitate homologous recombination (HR) in the S and G2 phases of the cell cycle.

What is this preprint about?

Because of its potential mutagenic effect, DNA damage is one of the most dangerous insults for the cell. Although the protein component of the DNA repair machinery has been relatively well documented, recent work has also identified (non-coding) RNA as a major contributor to fine-tune the DNA repair pathways. In 2017, the group of Dr. Fabrizio d’Adda di Fagagna showed that in mammalian cells, a novel class of long non-coding RNAs (dilncRNAs) is transcribed from broken ends upon DSB formation after resection, a process necessary to free up DNA ends before HR can occur. They evidenced that these dilncRNAs contribute to the DNA repair process both by acting as precursors for DNA damage-associated small non-coding RNAs (DDRNA, previously characterized in Francia et al., 2012) and through the recruitment of DDRNAs by RNA-RNA pairing (see Michelini et al., NCB, 2017). In their recent preprint, the same authors show that dilncRNAs enhance HR-mediated DNA repair in the HR-prone S and G2 phases of the cell cycle by recruiting major HR factors. Moreover, they provide evidence that RNAse H2 is in a complex with the HR proteins BRCA1, PALB2, BRCA2 and RAD51, and that this R-loop-resolving protein is essential to remove the DNA-damage induced DNA-RNA hybrids so that proper repair can occur.

My opinion: 

What I love about this preprint is that this study helps to put forward the notion that RNA molecules play crucial roles in processes commonly considered to be dominated solely by a protein system.

Specifically, in the nucleus, ephemeral RNA molecules act not only as messengers, but also as guides, supports, protectors, inhibitors or physical barriers, recruiters, or flag signs. The dilncRNAs help generic and abundant proteins, such as those of the DNA repair machinery, to make the right choice in the right place and time. Because these RNAs are so versatile and short-lived, they provide the perfect “LINC” between a robust response to damage and an elegant fine-tuning of the complex nuclear environment.

In the future, it would be interesting to determine how the formation of RNA:DNA hybrids per se contributes to the DNA repair process, especially since they have been reported to be both the cause and consequence of DNA damage. Furthermore, it will be important to study to a further degree how the breaks and their repair are influenced by the RNA species (either bound or not to the broken and resected DNA ends), and how the proteins that regulate the biogenesis and metabolism of these RNA species affect the repair process.

Further reading: 

1. Transient RNA-DNA Hybrids Are Required for Efficient Double-Strand Break Repair. Ohle, Tesorero et al., 2016, Cell, Volume 167, Issue 4, 1001 – 1013.e7
This paper used a yeast system (S. pombe) to show how resected ends are transcribed bidirectionally and serve as substrates for DNA-RNA hybrid formation. It conceptually led the way for the current study.

2. Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks. Michelini et al., 2017, Nature Cell Biology 19, pages 1400–1411.
In this paper, the authors beautifully show a role for RNA polymerase II at DNA breaks and advance the idea that non-coding RNA may play a crucial role in DSB repair.

3. The emerging role of RNAs in DNA damage repair. Hawley et al., 2017. Cell death and differentiation. (2017) 24, 580–587
A great review on how in the last few years we came to realize how RNAs are more important than initially thought for the DNA repair processes in the cell.

4. Site-specific DICER and DROSHA RNA products control the DNA damage response. Francia et al. Nature (2012) 488(7410): 231–235.
The initial paper characterizing the involvement of DDRNA in the DNA repair process, through the DICER and DROSHA proteins, but not other components of the RNAi machinery.


Posted on bioRxiv Jan, 29th, 2018. doi:


Tags: dilncrna, dna repair, dna:rna hybrid, homologous recombination, rnase h

Posted on: 19 March 2018 , updated on: 20 March 2018

Read preprint (No Ratings Yet)

Have your say

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

preLists in the cancer biology category:

Also in the cell biology category:

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.


List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.


List by Nadja Hümpfer et al.


The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!


List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.


List by Alex Eve

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020


List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.


List by Ana Dorrego-Rivas

BioMalPar XVI: Biology and Pathology of the Malaria Parasite

[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria


List by Dey Lab, Samantha Seah


Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.


List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20


List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.


List by Paul Gerald L. Sanchez and Stefano Vianello

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome


List by Hiral Shah

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)


List by Madhuja Samaddar et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019


List by Dey Lab


Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.


List by Sandra Malmgren Hill

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.


List by Rob Hynds

Cellular metabolism

A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.


List by Pablo Ranea Robles

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019


List by Dey Lab


This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.


List by Sandra Franco Iborra

ASCB/EMBO Annual Meeting 2018

This list relates to preprints that were discussed at the recent ASCB conference.


List by Dey Lab, Amanda Haage

Also in the molecular biology category: