Toxic R-loops: Cause or consequence of replication stress?

Transcription-replication conflicts (TRCs) represent a potential source of endogenous replication stress (RS) and genomic instability in eukaryotic cells but the mechanisms that underlie this instability remain poorly understood. Part of the problem could come from non-B DNA structures called R-loop...

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Bibliographic Details
Published in:DNA repair 2021-11, Vol.107, p.103199, Article 103199
Main Authors: Kemiha, Samira, Poli, Jérôme, Lin, Yea-Lih, Lengronne, Armelle, Pasero, Philippe
Format: Article
Language:English
Subjects:
Animals
DNA - metabolism
DNA Replication
DNA, Single-Stranded - metabolism
Genomic Instability
Humans
Life Sciences
R-Loop Structures
R-loops
Replication
RNA - metabolism
RNA:DNA hybrids
Transcription
Transcription, Genetic
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Summary:Transcription-replication conflicts (TRCs) represent a potential source of endogenous replication stress (RS) and genomic instability in eukaryotic cells but the mechanisms that underlie this instability remain poorly understood. Part of the problem could come from non-B DNA structures called R-loops, which are formed of a RNA:DNA hybrid and a displaced ssDNA loop. In this review, we discuss different scenarios in which R-loops directly or indirectly interfere with DNA replication. We also present other types of TRCs that may not depend on R-loops to impede fork progression. Finally, we discuss alternative models in which toxic RNA:DNA hybrids form at stalled forks as a consequence - but not a cause - of replication stress and interfere with replication resumption.
ISSN:1568-7864
1568-7856
1568-7856
DOI:10.1016/j.dnarep.2021.103199