The balancing act of R-loop biology: The good, the bad, and the ugly.

Youssef A. Hegazy,Chrishan M. Fernando,Elizabeth J. Tran

doi:10.1074/jbc.rev119.011353

Youssef A. Hegazy, Chrishan M. Fernando + Show 1 more

Open Access

https://doi.org/10.1074/jbc.rev119.011353

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Abstract

An R-loop is a three-stranded nucleic acid structure that consists of a DNA:RNA hybrid and a displaced strand of DNA. R-loops occur frequently in genomes and have significant physiological importance. They play vital roles in regulating gene expression, DNA replication, and DNA and histone modifications. Several studies have uncovered that R-loops contribute to fundamental biological processes in various organisms. Paradoxically, although they do play essential positive functions required for important biological processes, they can also contribute to DNA damage and genome instability. Recent evidence suggests that R-loops are involved in a number of human diseases, including neurological disorders, cancer, and autoimmune diseases. This review focuses on the molecular basis for R-loop-mediated gene regulation and genomic instability and briefly discusses methods for identifying R-loops in vivo It also highlights recent studies indicating the role of R-loops in DNA double-strand break repair with an updated view of much-needed future goals in R-loop biology.

Highlights

An R-loop is a three-stranded nucleic acid structure that consists of a DNA:RNA hybrid and a displaced strand of DNA
This review focuses on the molecular basis for R-loop–mediated gene regulation and genomic instability and briefly discusses methods for identifying R-loops in vivo
In vivo R-loop formation was demonstrated using Escherichia coli strains that had a null mutation for topA, the gene that encodes topoisomerase I (TOPO I),2 or a temperature-sensitive mutation for gyrB, the

Summary

Introduction

An R-loop is a three-stranded nucleic acid structure that consists of a DNA:RNA hybrid and a displaced strand of DNA. R-loops occur frequently in genomes and have significant physiological importance They play vital roles in regulating gene expression, DNA replication, and DNA and histone modifications. This review focuses on the molecular basis for R-loop–mediated gene regulation and genomic instability and briefly discusses methods for identifying R-loops in vivo. It highlights recent studies indicating the role of R-loops in DNA double-strand break repair with an updated view of muchneeded future goals in R-loop biology. As mentioned later in this review, inefficient repair of DNA breaks during the process of CSR can lead to genomic instability [11], CSR remains a vital physiological process in which R-loops play an important role to allow for antibody class diversification. R-loop formation and stabilization at the COOLAIR promoter region was found to reduce the expression of these antisense

Methods

Conclusion