R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde.
Int J Mol Sci
; 22(16)2021 Aug 17.
Article
em En
| MEDLINE
| ID: mdl-34445553
ABSTRACT
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 RNADNA 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.
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Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
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Instabilidade Genômica
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Montagem e Desmontagem da Cromatina
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Reparo do DNA
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Replicação do DNA
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Estruturas R-Loop
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article