Functional conservation and divergence of Arabidopsis VENOSA4 and human SAMHD1 in DNA repair

Heliyon, Год журнала: 2024, Номер 11(1), С. e41019 - e41019

Опубликована: Дек. 10, 2024

Язык: Английский

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SIRT1 Prevents R-Loops during Chronological Aging by Modulating DNA Replication at rDNA Loci

Cells, Год журнала: 2023, Номер 12(22), С. 2630 - 2630

Опубликована: Ноя. 15, 2023

In metazoans, the largest sirtuin, SIRT1, is a nuclear protein implicated in epigenetic modifications, circadian signaling, DNA recombination, replication, and repair. Our previous studies have demonstrated that SIRT1 binds replication origins inhibits initiation from group of potential sites (dormant origins). We studied effects aging activity on origin usage incidence transcription–replication collisions (creating R-loop structures) adult human cells obtained at different time points during chronological cancer cells. primary, untransformed cells, declined prevalence R-loops rose with aging. Both reduction increased abundance were also observed passage primary culture. All regardless donor age or transformation status, reacted to short-term, acute chemical inhibition activation excessive events coincident an R-loops. However, activated dormant origins, genome-wide, long-term proliferation mutated depleted whereas, aging-associated SIRT1-mediated was restricted rDNA loci. These observations suggest associated decline relax regulatory networks protect against excess mechanisms protecting replication–transcription loci manifest as differentially enhanced sensitivities

Язык: Английский

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Minichromosome Maintenance Proteins: From DNA Replication to the DNA Damage Response

Cells, Год журнала: 2024, Номер 14(1), С. 12 - 12

Опубликована: Дек. 26, 2024

The DNA replication machinery is highly conserved from bacteria to eukaryotic cells. Faithful vital for cells transmit accurate genetic information the next generation. However, both internal and external damages threaten intricate process, leading activation of damage response (DDR) system. Dysfunctional DDR are a source genomic instability, causing heritable mutations that drive cancer evolutions. family minichromosome maintenance (MCM) proteins plays an important role not only in but also DDR. Here, we will review current strides MCM these integrated processes as well acetylation/deacetylation value MCMs biomarkers cancer.

Язык: Английский

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Maintenance of genome integrity under physical constraints

Chromosoma, Год журнала: 2024, Номер 133(1), С. 1 - 3

Опубликована: Янв. 1, 2024

Язык: Английский

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Pathological R-loops in bacteria from engineered expression of endogenous antisense RNAs whose synthesis is ordinarily terminated by Rho

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 20, 2024

Abstract In many bacteria, the essential factors Rho and NusG mediate termination of synthesis nascent transcripts (including antisense RNAs) which are not being simultaneously translated. It has been proposed that in Rho’s absence toxic RNA-DNA hybrids (R-loops) may be generated from untranslated transcripts; genome-wide mapping studies Escherichia coli have identified putative loci R-loop formation more than 100 endogenous synthesized only a Rho-deficient strain. Here we provide evidence engineered expression wild-type E. several such individual regions on plasmid or chromosome generates R-loops that, an RNase H-modulated manner, serve to disrupt genome integrity. inhibition was associated with increased prevalence also Xanthomonas oryzae pv. Caulobacter crescentus . Our results confirm role bacterial genera for prevention pervasive yet cryptic transcripts. Engineered R-looped useful both site-specific impediments chromosomal replication mechanisms their resolution.

Язык: Английский

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Functional conservation and divergence of Arabidopsis VENOSA4 and human SAMHD1 in DNA repair

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 31, 2024

SUMMARY The human deoxyribonucleoside triphosphatase (dNTPase) Sterile alpha motif and histidine-aspartate domain containing protein 1 (SAMHD1) has a dNTPase-independent role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Here, we show that VENOSA4 (VEN4), the probable Arabidopsis thaliana ortholog of SAMHD1, also functions DSB repair HR. ven4 loss-of-function mutants showed increased ploidy deregulated genes, suggesting damage accumulation. Hydroxyurea, which blocks replication generates DSBs, induced VEN4 expression. were hypersensitive to hydroxyurea, with decreased Metabolomic analysis strong ven4-0 mutant revealed depletion metabolites associated responses. In contrast no evident involvement preventing R-loop Our study thus reveals functional conservation SAMHD1. One sentence summary Human SAMHD1 is involved dNTP metabolism repair; latter function conserved VEN4, its likely ortholog.

Язык: Английский

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Error-Prone DNA Mismatch and Base Excision Repair in the Somatic Hypermutation of Antibody Variable Regions

Elsevier eBooks, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

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