Abstract
Genome integrity can be threatened by various endogenous or exogenous events. To counteract these stressors, the DNA damage response network contributes to the prevention and/or repair of genomic DNA damage and serves an essential function in cellular survival. DNA binding proteins are involved in this network. Recently, several RNA-binding proteins (RBPs) that are recruited to DNA damage sites have been shown to be direct players in the prevention or repair of DNA damage. In addition, non-coding RNAs, themselves, are involved in the RNA-mediated DNA repair system. Furthermore, RNA modification such as m6A methylation might also contribute to the ultraviolet-responsive DNA damage response. Accumulating evidence suggests that RNA metabolism is more deeply involved in diverse cellular functions than previously expected, and is also intricately associated with the maintenance of genome integrity. In this review, we highlight the roles of RBPs in the maintenance of genome integrity.
Highlights
Genome integrity is a fundamental issue that is associated with cell survival
Ontology analysis of DNA- and RNA-binding proteins (DRBPs) indicated that many of these might be involved in unexpected biological processes including the DNA-damage response (DDR), apoptosis, and responses to extreme temperature [6]
Many RNA-binding proteins (RBPs) have the potential to bind DNA, and some are involved in DNA repair or accumulate at sites of DNA damage
Summary
Genome integrity is a fundamental issue that is associated with cell survival. To counteract stress-induced DNA damage such as aberrant DNA replication, transcription, and uncontrolled cell division, the coordination of numerous proteins is required to maintain genome integrity for organism survival. RNA-binding proteins (RBPs) have emerged as important players and coordinators in the maintenance of genome integrity. In addition to binding RNA species, RBPs can interact with various functional proteins, suggesting undiscovered roles in cellular processes including the maintenance of genome integrity. Accumulating knowledge suggests that the functional domains of proteins with both DNA- and RNA-binding capacity are important for the modulation of cellular homeostasis, including gene expression, cell proliferation, DDR, and genome stability. Advanced analytical techniques such as RNA deep sequencing and single cell analysis have been providing us with unexpected functions of RBPs and RNA species in genome maintenance. In this review, we focus on aspects of the genome maintenance function of RBPs, especially regarding R-loop formation, telomerase activity, DNA damage response, and replication
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