G-quadruplex resolution: From molecular mechanisms to physiological relevance

DNA repair, vol. 130, pp. 103552

Abstract

Guanine-rich DNA sequences can fold into stable four-stranded structures called G-quadruplexes or G4s. Research in the past decade demonstrated that G4 structures are widespread in the genome and prevalent in regulatory regions of actively transcribed genes. The formation of G4s has been tightly linked to important biological processes including regulation of gene expression and genome maintenance. However, they can also pose a serious threat to genome integrity especially by impeding DNA replication, and G4-associated somatic mutations have been found accumulated in the cancer genomes. Specialised DNA helicases and single stranded DNA binding proteins that can resolve G4 structures play a crucial role in preventing genome instability. The large variety of G4 unfolding proteins suggest the presence of multiple G4 resolution mechanisms in cells. Recently, there has been considerable progress in our detailed understanding of how G4s are resolved, especially during DNA replication. In this review, we first discuss the current knowledge of the genomic G4 landscapes and the impact of G4 structures on DNA replication and genome integrity. We then describe the recent progress on the mechanisms that resolve G4 structures and their physiological relevance. Finally, we discuss therapeutic opportunities to target G4 structures.

Authors 2

1. Koichi Sato corresponding

   University Medical Center Utrecht · Royal Netherlands Academy of Arts and Sciences · Oncode Institute · Hubrecht Institute for Developmental Biology and Stem Cell Research

   Affiliation as printed

   Oncode Institute, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: k.sato@hubrecht.eu

   Oncode Institute, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, the Netherlands

2. Puck Knipscheer corresponding Aachen Department of Human Genetics

   University Medical Center Utrecht · Leiden University Medical Center · Royal Netherlands Academy of Arts and Sciences · Oncode Institute

   Affiliation as printed

   Oncode Institute, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, the Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: p.knipscheer@hubrecht.eu

   Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands

   Oncode Institute, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, the Netherlands