title: Replication Fork Protection Factors Controlling R-Loop Bypass and Suppression.
abstract: Replication-transcription conflicts have been a well-studied source of genome instability for many years and have frequently been linked to defects in RNA processing. However, recent characterization of replication fork-associated proteins has revealed that defects in fork protection can directly or indirectly stabilize R-loop structures in the genome and promote transcription-replication conflicts that lead to genome instability. Defects in essential DNA replication-associated activities like topoisomerase, or the minichromosome maintenance (MCM) helicase complex, as well as fork-associated protection factors like the Fanconi anemia pathway, both appear to mitigate transcription-replication conflicts. Here, we will highlight recent advances that support the concept that normal and robust replisome function itself is a key component of mitigating R-loop coupled genome instability.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, 675 West 10th Ave., Vancouver, BC V5Z1L3, Canada. echang@bccrc.ca.
authors.forename: Emily Yun-Chia
authors.initials: EY
authors.lastname: Chang
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, 675 West 10th Ave., Vancouver, BC V5Z1L3, Canada. pstirling@bccrc.ca.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Stirling
keywords: DNA repair; DNA replication stress; R-loop; transcription–replication conflict