Genomic Instability of G-Quadruplex Sequences in Escherichia coli: Roles of DinG, RecG, and RecQ Helicases DOI Open Access

Virali J. Parekh,

Grzegorz Węgrzyn, Véronique Arluison

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(9), P. 1720 - 1720

Published: Aug. 29, 2023

Guanine-rich DNA can fold into highly stable four-stranded structures called G-quadruplexes (G4). Originally identified in sequences from telomeres and oncogene promoters, they alter metabolism. Indeed, G4-forming represent obstacles for the polymerase, with important consequences cell life as may lead to genomic instability. To understand their role bacterial instability, different G-quadruplex-forming repeats were cloned an Escherichia coli genetic system that reports frameshifts complete or partial deletions of repeat when G-tract comprises either leading lagging template strand during replication. These formed single-stranded but not naturally supercoiled double-stranded DNA. Nevertheless, transcription promoted G-quadruplex formation resulting R-loop (G3T)4 (G3T)8 repeats. Depending on background sequence propensity structure formation, mutation rates varied by five orders magnitude. Furthermore, while vitro approaches have shown helicases resolve G4, it is still unclear whether G4 unwinding vivo. Here, we show a recG decreased rates, deficiencies structure-specific DinG RecQ increased rates. results suggest promotes instability bacteria play controlling this process

Language: Английский

G-Quadruplex Forming DNA Sequence Context Is Enriched around Points of Somatic Mutations in a Subset of Multiple Myeloma Patients DOI Open Access
Anna S. Zhuk, Elena I. Stepchenkova, Irina V. Zotova

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5269 - 5269

Published: May 12, 2024

Multiple myeloma (MM) is the second most common hematological malignancy, which remains incurable despite recent advances in treatment strategies. Like other forms of cancer, MM characterized by genomic instability, caused defects DNA repair. Along with mutations repair genes and genotoxic drugs used to treat MM, non-canonical secondary structures (four-stranded G-quadruplex structures) can affect accumulation somatic chromosomal abnormalities tumor cells patients. Here, we tested hypothesis that may influence distribution We sequenced exomes normal 11 patients analyzed data for presence G4 context around points mutations. To identify molecular mechanisms could mutational profile tumors, also signatures as well germline specific SNPs or regulating unwinding. In several patients, found sites are frequently located regions context. This pattern correlated variants these discuss possible implications mutation specificity propose extent enrichment be a novel metric characterizing processes tumors.

Language: Английский

Citations

2
Genomic Instability of G-Quadruplex Sequences in Escherichia coli: Roles of DinG, RecG, and RecQ Helicases DOI Open Access

Virali J. Parekh,

Grzegorz Węgrzyn, Véronique Arluison

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(9), P. 1720 - 1720

Published: Aug. 29, 2023

Guanine-rich DNA can fold into highly stable four-stranded structures called G-quadruplexes (G4). Originally identified in sequences from telomeres and oncogene promoters, they alter metabolism. Indeed, G4-forming represent obstacles for the polymerase, with important consequences cell life as may lead to genomic instability. To understand their role bacterial instability, different G-quadruplex-forming repeats were cloned an Escherichia coli genetic system that reports frameshifts complete or partial deletions of repeat when G-tract comprises either leading lagging template strand during replication. These formed single-stranded but not naturally supercoiled double-stranded DNA. Nevertheless, transcription promoted G-quadruplex formation resulting R-loop (G3T)4 (G3T)8 repeats. Depending on background sequence propensity structure formation, mutation rates varied by five orders magnitude. Furthermore, while vitro approaches have shown helicases resolve G4, it is still unclear whether G4 unwinding vivo. Here, we show a recG decreased rates, deficiencies structure-specific DinG RecQ increased rates. results suggest promotes instability bacteria play controlling this process

Language: Английский

Citations

2