Endogenous Bos taurus RECQL is predominantly monomeric and more active than oligomers

Liu, Na-Nv; Song, Ze-Yu; Guo, Hai-Lei; Yin, Hu; Chen, Wei-Fei; Dai, Yang-Xue; Xin, Ben-Ge; Ai, Xia; Ji, Lei; Qingman, Wang; Hou, Xi-Miao; Dou, S. X.; Réty, S.; Xi, Xu-Guang

doi:10.1016/j.celrep.2021.109688

Cited by 11 publications

(6 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, most recently, Xi’s lab reported that the unwinding activity of Bos taurus RECQ1 was modulated by its oligomeric states. In addition, both monomeric BtRECQ1 and monomeric human RECQ1 unfolded intramolecular G4 DNA as efficiently as human BLM helicase ( Liu N.-N. et al, 2021 ). There are evidences suggest that RECQ1 can function through interaction with G4s.…”

Section: G-quadruplex Unwinding Helicases and Their Functionsmentioning

confidence: 99%

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

Liu

Zhu

Wang

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

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.

show abstract

Section: G-quadruplex Unwinding Helicases and Their Functionsmentioning

confidence: 99%

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

Liu

Zhu

Wang

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…The ability of RECQL1 to restart forks through branch migration of a reversed fork was shown to require its ATPase activity ( 14 ). While the p.A459S mutation lies outside the RECQL1 helicase domain, it has been previously demonstrated that mutating conserved cysteine residues within the ZBD compromises both its ATPase and DNA unwinding activities ( 11 , 12 ). In keeping with this, we have shown that the p.A459S mutation also substantially reduced the ATPase, DNA unwinding, and branch-migrating activities of RECQL1.…”

Section: Discussionmentioning

confidence: 99%

“…It can also catalyze branch migration of Holliday junctions and D-loops, unwind G4 structures, and promote single-strand DNA annealing (SSA). However, unlike other human RecQ helicases, it acts poorly to unwind RNA:DNA hybrids or displace Rad51 bound to ssDNA ( 11 , 12 ). Despite its demonstrated biochemical activities, mice devoid of this enzyme are phenotypically normal ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1

Abu‐Libdeh¹,

Jhujh²,

Dhar³

et al. 2022

Journal of Clinical Investigation

View full text Add to dashboard Cite

Despite being the first homolog of the bacterial RecQ helicase to be identified in humans the function of RECQL1 remains poorly characterised. Furthermore, unlike other members of the human RECQ family of helicases, mutations in RECQL1 have not been associated with a genetic disease. Here we identify two families with a novel genome instability disorder, named RECON (RECql ONe) Syndrome caused by biallelic mutations in the RECQL gene. The affected individuals exhibit short stature, progeroid facial features, a hypoplastic nose, xeroderma and skin photosensitivity. Affected individuals were homozygous for the same missense mutation in RECQL1 (p.Ala459Ser) located within its zinc binding domain. Biochemical analysis of the mutant RECQL1 protein revealed that the p.A459S missense mutation compromised its ATPase, helicase and fork restoration activity, whilst its capacity to promote single-strand DNA annealing was largely unaffected. At the cellular level, this mutation in RECQL1 gave rise to a defect in the ability to repair DNA damage induced by exposure to topoisomerase poisons and a failure of DNA replication to progress efficiently in the presence of abortive topoisomerase lesions. Taken together, RECQL1 is the fourth member of the RecQ family of helicases to be associated with a human genome instability disorder.

show abstract

“…The malachite green assay (MAK113; Sigma‐Aldrich) was used to test the ATP hydrolysis activity of ToPif1 and its mutants by measuring the release of inorganic phosphate as previously described (Liu et al , 2021). Briefly, 100 nM purified protein and ATP (concentrations ranging from 0 μM to 400 μM) were incubated with or without a 1 mM DNA effector (S 18 H 11 , sequence were shown in Table EV1) using a VICTOR Nivo Multimode Microplate Reader (PerkinElmer, Waltham, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Structural mechanism underpinning Thermus oshimai Pif1‐mediated G‐quadruplex unfolding

et al. 2022

Self Cite

View full text Add to dashboard Cite

G-quadruplexes (G4s) are unusual stable DNA structures that cause genomic instability. To overcome the potential barriers formed by G4s, cells have evolved different families of proteins that unfold G4s. Pif1 is a DNA helicase from superfamily 1 (SF1) conserved from bacteria to humans with high G4-unwinding activity. Here, we present the first X-ray crystal structure of the Thermus oshimai Pif1 (ToPif1) complexed with a G4. Our structure reveals that ToPif1 recognizes the entire native G4 via a cluster of amino acids at domains 1B/2B which constitute a G4-Recognizing Surface (GRS). The overall structure of the G4 maintains its three-layered propeller-type G4 topology, without significant reorganization of G-tetrads upon protein binding. The three G-tetrads in G4 are recognized by GRS residues mainly through electrostatic, ionic interactions, and hydrogen bonds formed between the GRS residues and the ribose-phosphate backbone. Compared with previously solved structures of SF2 helicases in complex with G4, our structure reveals how helicases from distinct superfamilies adopt different strategies for recognizing and unfolding G4s.

show abstract

Endogenous Bos taurus RECQL is predominantly monomeric and more active than oligomers

Cited by 11 publications

References 37 publications

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

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

RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1

Structural mechanism underpinning Thermus oshimai Pif1‐mediated G‐quadruplex unfolding

Contact Info

Product

Resources

About