RT Generic T1 The Role of Replication-Associated Repair Factors on R-Loops A1 Bhatia, Vaibhav A1 Herrera-Moyano, Emilia A1 Aguilera, Andres A1 Gomez-Gonzalez, Belen K1 genetic instability K1 DNA-RNA hybrids K1 Fanconi anemia K1 BRCA K1 replication stress K1 cancer K1 Mediated genome instability K1 Dna-rna hybrids K1 Cancer susceptibility protein K1 Transcriptional pause sites K1 Fanconi anemia/brca pathway K1 Common fragile sites K1 Cross-link repair K1 Saccharomyces-cerevisiae K1 Fork progression K1 Rna/dna hybrids AB 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. PB Mdpi ag SN 2073-4425 YR 2017 FD 2017-07-01 LK http://hdl.handle.net/10668/19261 UL http://hdl.handle.net/10668/19261 LA en DS RISalud RD Apr 6, 2025