R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde.

DNA damage R-T conflicts R-loops RNA:DNA hybrids chromatin remodelers genome stability histone modifiers

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
17 Aug 2021
Historique:
received: 14 07 2021
revised: 04 08 2021
accepted: 12 08 2021
entrez: 27 8 2021
pubmed: 28 8 2021
medline: 14 9 2021
Statut: epublish

Résumé

Since their discovery, R-loops have been associated with both physiological and pathological functions that are conserved across species. R-loops are a source of replication stress and genome instability, as seen in neurodegenerative disorders and cancer. In response, cells have evolved pathways to prevent R-loop accumulation as well as to resolve them. A growing body of evidence correlates R-loop accumulation with changes in the epigenetic landscape. However, the role of chromatin modification and remodeling in R-loops homeostasis remains unclear. This review covers various mechanisms precluding R-loop accumulation and highlights the role of chromatin modifiers and remodelers in facilitating timely R-loop resolution. We also discuss the enigmatic role of RNA:DNA hybrids in facilitating DNA repair, epigenetic landscape and the potential role of replication fork preservation pathways, active fork stability and stalled fork protection pathways, in avoiding replication-transcription conflicts. Finally, we discuss the potential role of several Chro-Mates (chromatin modifiers and remodelers) in the likely differentiation between persistent/detrimental R-loops and transient/benign R-loops that assist in various physiological processes relevant for therapeutic interventions.

Identifiants

pubmed: 34445553
pii: ijms22168850
doi: 10.3390/ijms22168850
pmc: PMC8396322
pii:
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

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Auteurs

Sidrit Uruci (S)

Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.

Calvin Shun Yu Lo (CSY)

Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.

David Wheeler (D)

Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Nitika Taneja (N)

Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.

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