Publication: The Role of Replication-Associated Repair Factors on R-Loops
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Date
2017-07-01
Authors
Bhatia, Vaibhav
Herrera-Moyano, Emilia
Aguilera, Andres
Gomez-Gonzalez, Belen
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Mdpi ag
Abstract
The nascent RNA can reinvade the DNA double helix to form a structure termed the R-loop, where a single-stranded DNA (ssDNA) is accompanied by a DNA-RNA hybrid. Unresolved R-loops can impede transcription and replication processes and lead to genomic instability by a mechanism still not fully understood. In this sense, a connection between R-loops and certain chromatin markers has been reported that might play a key role in R-loop homeostasis and genome instability. To counteract the potential harmful effect of R-loops, different conserved messenger ribonucleoprotein (mRNP) biogenesis and nuclear export factors prevent R-loop formation, while ubiquitously-expressed specific ribonucleases and DNA-RNA helicases resolve DNA-RNA hybrids. However, the molecular events associated with R-loop sensing and processing are not yet known. Given that R-loops hinder replication progression, it is plausible that some DNA replication-associated factors contribute to dissolve R-loops or prevent R-loop mediated genome instability. In support of this, R-loops accumulate in cells depleted of the BRCA1, BRCA2 or the Fanconi anemia (FA) DNA repair factors, indicating that they play an active role in R-loop dissolution. In light of these results, we review our current view of the role of replication-associated DNA repair pathways in preventing the harmful consequences of R-loops.
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Keywords
genetic instability, DNA-RNA hybrids, Fanconi anemia, BRCA, replication stress, cancer, Mediated genome instability, Dna-rna hybrids, Cancer susceptibility protein, Transcriptional pause sites, Fanconi anemia/brca pathway, Common fragile sites, Cross-link repair, Saccharomyces-cerevisiae, Fork progression, Rna/dna hybrids