TY - JOUR
T1 - G-quadruplex resolution
T2 - From molecular mechanisms to physiological relevance
AU - Sato, Koichi
AU - Knipscheer, Puck
N1 - Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
KW - G-Quadruplexes
KW - DNA Replication
KW - DNA Helicases/metabolism
KW - DNA-Binding Proteins/metabolism
KW - Regulatory Sequences, Nucleic Acid
U2 - 10.1016/j.dnarep.2023.103552
DO - 10.1016/j.dnarep.2023.103552
M3 - Book/Film/Article review
C2 - 37572578
SN - 1568-7856
VL - 130
SP - 103552
JO - DNA repair
JF - DNA repair
ER -