Replication protein A plays multifaceted roles complementary to specialized helicases in processing G-quadruplex DNA

Guo, Tingting; Zheng, Yating; Lai, Chang-Wei; Sun, Bo; Xi, Xu-Guang; Hou, Xi-Miao

doi:10.1016/j.isci.2021.102493

Cited by 13 publications

(13 citation statements)

References 52 publications

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“…Furthermore, as the stability of the qDNA structure increased, the fraction of unfolded molecules decreased only slightly in the case of antiparallel qDNA but was reduced significantly in the case of G-quadruplexes with a parallel conformation. Additional evidence was later obtained by another investigation employing smFRET to support the conclusion that antiparallel conformations of qDNA are unwound more efficiently . Furthermore, this study found qDNA structures with shorter loops were barely unfolded and reaffirmed the hypothesis that Pif1 is highly sensitive to the thermal stability of the qDNA.…”

Section: G-quadruplex Biology: Ally or Enemy To Genomic Maintenance?supporting

confidence: 72%

“…Building upon these earlier investigations, a subsequent series of experiments performed using smFRET explored the effect of the length of the loops present in a qDNA molecule on its thermal stability. Surprisingly, it was also found that RPA quickly linearizes DNA before it can be folded into qDNA structures . In the majority of instances, the FRET efficiency of the linearized DNA did not increase despite being exposed to the correct conditions for qDNA folding.…”

Section: G-quadruplex Biology: Ally or Enemy To Genomic Maintenance?mentioning

confidence: 99%

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Understanding G-Quadruplex Biology and Stability Using Single-Molecule Techniques

Kusi-Appauh,

Ralph,

van Oijen

et al. 2023

J. Phys. Chem. B

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The link between the chemical stability of Gquadruplex (qDNA) structures and their roles in eukaryotic genomic maintenance processes has been an area of interest now for several decades. This Review seeks to demonstrate how single-molecule force-based techniques can provide insight into the mechanical stabilities of a variety of qDNA structures as well as their ability to interconvert between different conformations under conditions of stress. Atomic force microscopy (AFM) and magnetic and optical tweezers have been the primary tools used in these investigations and have been used to examine both free and ligand-stabilized Gquadruplex structures. These studies have shown that the degree of stabilization of G-quadruplex structures has a significant effect on the ability of nuclear machinery to bypass these roadblocks on DNA strands. This Review will illustrate how various cellular components including replication protein A (RPA), Bloom syndrome protein (BLM), and Pif1 helicases are capable of unfolding qDNA. Techniques such as single-molecule fluorescence resonance energy transfer (smFRET), often in conjunction with the aforementioned force-based techniques, have proven extremely effective at elucidating the factors underpinning the mechanisms by which these proteins unwind qDNA structures. We will provide insight into how single-molecule tools have facilitated the direct visualization of qDNA roadblocks and also showcase results obtained from experiments designed to examine the ability of G-quadruplexes to limit the access of specific cellular proteins normally associated with telomeres.

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Section: G-quadruplex Biology: Ally or Enemy To Genomic Maintenance?supporting

confidence: 72%

Section: G-quadruplex Biology: Ally or Enemy To Genomic Maintenance?mentioning

confidence: 99%

Understanding G-Quadruplex Biology and Stability Using Single-Molecule Techniques

Kusi-Appauh,

Ralph,

van Oijen

et al. 2023

J. Phys. Chem. B

View full text Add to dashboard Cite

show abstract

“…Besides its ability to dissolve dHJ, BLM binds and unwinds G4 structures in vitro [61,102]. Sister chromatid exchange events (SCEs) are a byproduct of DSB or collapsed replication forks that are repaired via HR [117,118]. Strand-seq analysis revealed that SCEs are enriched at G4 motifs in BLM-deficient cells indicating that G4 structures can trigger SCE in the absence of BLM [64].…”

Section: Pathwaymentioning

confidence: 99%

The Relevance of G-Quadruplexes for DNA Repair

Linke

Limmer

Juranek

et al. 2021

IJMS

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DNA molecules can adopt a variety of alternative structures. Among these structures are G-quadruplex DNA structures (G4s), which support cellular function by affecting transcription, translation, and telomere maintenance. These structures can also induce genome instability by stalling replication, increasing DNA damage, and recombination events. G-quadruplex-driven genome instability is connected to tumorigenesis and other genetic disorders. In recent years, the connection between genome stability, DNA repair and G4 formation was further underlined by the identification of multiple DNA repair proteins and ligands which bind and stabilize said G4 structures to block specific DNA repair pathways. The relevance of G4s for different DNA repair pathways is complex and depends on the repair pathway itself. G4 structures can induce DNA damage and block efficient DNA repair, but they can also support the activity and function of certain repair pathways. In this review, we highlight the roles and consequences of G4 DNA structures for DNA repair initiation, processing, and the efficiency of various DNA repair pathways.

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“…However, their cooperation with helicases has not been well studied. Recently, Hou’s group used smFRET to study the relationship between RPA, PIF1, and BLM ( Wang et al, 2021 ). They found that both RPA and helicases were need for stable G4 DNA unfolding, and RPA played a complementary role for G4 unfolding by helicases ( Wang et al, 2021 ).…”

Section: Representative Research Methods To Reveal Molecular Mechanismsmentioning

confidence: 99%

The Cellular Functions and Molecular Mechanisms of G-Quadruplex Unwinding Helicases in Humans

Liu

Zhu

Wang

et al. 2021

Front. Mol. Biosci.

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G-quadruplexes (G4s) are stable non-canonical secondary structures formed by G-rich DNA or RNA sequences. They play various regulatory roles in many biological processes. It is commonly agreed that G4 unwinding helicases play key roles in G4 metabolism and function, and these processes are closely related to physiological and pathological processes. In recent years, more and more functional and mechanistic details of G4 helicases have been discovered; therefore, it is necessary to carefully sort out the current research efforts. Here, we provide a systematic summary of G4 unwinding helicases from the perspective of functions and molecular mechanisms. First, we provide a general introduction about helicases and G4s. Next, we comprehensively summarize G4 unfolding helicases in humans and their proposed cellular functions. Then, we review their study methods and molecular mechanisms. Finally, we share our perspective on further prospects. We believe this review will provide opportunities for researchers to reach the frontiers in the functions and molecular mechanisms of human G4 unwinding helicases.

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Replication protein A plays multifaceted roles complementary to specialized helicases in processing G-quadruplex DNA

Cited by 13 publications

References 52 publications

Understanding G-Quadruplex Biology and Stability Using Single-Molecule Techniques

Understanding G-Quadruplex Biology and Stability Using Single-Molecule Techniques

The Relevance of G-Quadruplexes for DNA Repair

The Cellular Functions and Molecular Mechanisms of G-Quadruplex Unwinding Helicases in Humans

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