The role of chromatin at transcription-replication conflicts as a genome safeguard

Abstract

DNA replication ensures the correct copying of the genome and the faithful transfer of the genetic information to the offspring. However, obstacles to replication fork (RF) progression cause RF stalling and compromise efficient genome duplication. Since replication uses the same DNA template as transcription, both transcription and replication must be coordinated to prevent Transcription-Replication Conflicts (TRCs) that could stall RF progression. Several factors contribute to limit the occurrence of such conflicts and their harmful impact on genome integrity. Increasing evidence indicates that chromatin homeostasis plays a key role in the cellular response to TRCs as well as in the preservation of genome integrity. Indeed, chromatin regulating enzymes are frequently mutated in cancer cells, a common characteristic of which is genome instability. Therefore, understanding the role of chromatin in TRC occurrence and resolution may help identify the molecular mechanism by which chromatin protects genome integrity, and the causes and physiological relevance of the high mutation rates of chromatin regulating factors in cancer. Here we review the current knowledge in the field, as well as the perspectives and future applications.