Emerging role for R-loops in chromosome segregation.

Abstract

R-loops are evolutionarily conserved three-stranded nucleic acid structures formed when a nascent RNA transcript hybridizes with its complementary DNA strand, thereby exposing the non-template strand as single-stranded DNA. Traditionally viewed as a by-product of transcription, R-loops are now recognized as critical regulators of diverse cellular processes, including gene expression, DNA replication, damage and repair, telomere length regulation, mitochondrial function and chromosome segregation. Here, we review studies that define the role of R-loops in ensuring faithful chromosome segregation during cell division and discuss how defects in R-loop dynamics lead to kinetochore (centromeric DNA and associated proteins) dysfunction and chromosomal instability. Taken together, these studies suggest that R-loops function as double-edged swords necessary for accurate chromosome segregation under physiological conditions, yet are deleterious if not resolved and improperly regulated. Given that R-loops have been associated with various diseases, targeting R-loop dynamics may offer novel therapeutic strategies for the treatment of diseases such as cancer.