Proofreading exonuclease activity of replicative polymerase epsilon promotes cellular tolerance to arabinosides in CTF18-dependent and -independent manner

Genome Instability & Disease, Год журнала: 2024, Номер 5(2), С. 76 - 88

Опубликована: Апрель 1, 2024

Abstract Ara-A, Ara-C, Ara-G, and Ara-T are arabinose sugars combined with adenine, cytosine, guanine, thymine bases, respectively. These drugs clinically important as these commonly used anti-viral anti-cancer drugs. an arabinoside, serves a chain terminator of deoxyribonucleic acid (DNA) replication by interfering after it is incorporated at the 3′ end nascent DNA, thereby restricting proliferation viruses cancer cells. The Ara-CMP efficiently removed proofreading exonuclease activity polymerase epsilon (Polε), in which alternative clamp loader CTF18 plays pivotal role. However, requirement for removal other arabinosides from DNA remains unclear. Here, we explored repair pathways responsible cellular tolerance to Ara-A found that cells deficient Polε ( POLE1 exo−/− ) showed highest sensitivity Ara-A. This was also required Ara-G Ara-T. −/− higher than wild-type cells, though critically lower Similar trends were observed results indicate activity, Polε-mediated Ara-C but does not play critical roles In this study, unveiled difference between (Ara-A, Ara-T) DNA.

Язык: Английский

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Pold4 subunit of replicative polymerase δ promotes fork slowing at broken templates

DNA repair, Год журнала: 2024, Номер 139, С. 103688 - 103688

Опубликована: Апрель 24, 2024

Язык: Английский

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Dominant roles of BRCA1 in cellular tolerance to a chain-terminating nucleoside analog, alovudine

DNA repair, Год журнала: 2024, Номер 137, С. 103668 - 103668

Опубликована: Март 5, 2024

Язык: Английский

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RAD18‐ and BRCA1‐dependent pathways promote cellular tolerance to the nucleoside analog ganciclovir

Genes to Cells, Год журнала: 2024, Номер 29(11), С. 935 - 950

Опубликована: Авг. 22, 2024

Ganciclovir (GCV) is a clinically important drug as it used to treat viral infections. GCV incorporated into the DNA during replication, where interferes with subsequent replication on GCV-incorporated templates. However, effects of host genome and mechanisms underlying cellular tolerance remain unclear. In this study, we explored these using collection mutant DT40 cells. We identified RAD17

Язык: Английский

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The flap endonuclease-1 mediated maturation of Okazaki fragments is critical for the cellular tolerance to remdesivir

DNA repair, Год журнала: 2024, Номер 144, С. 103773 - 103773

Опубликована: Окт. 9, 2024

Язык: Английский

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DNA Polymerase Locks Replication Fork Under Stress

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

Опубликована: Окт. 10, 2024

Replication of DNA requires the parental to be unwound allow genetic information faithfully duplicated by replisome. While this function is usually shared a host proteins in replisome, notably polymerase (DNAP) and helicase, consequence DNAP synthesizing while decoupled from helicase remains not well understood. The unwinding downstream poses significant stress DNAP, interaction between replication fork may affect restart. In work, we examined consequences working against fork. We found that prolonged exposure inactivates replication. Surprisingly, inactivation was often accompanied strong with leading lagging strands at fork, locking place. demonstrated forward translocation, exonuclease activity which allows move reverse, essential protecting inactivation. Furthermore, configuration reversible subsequent addition helicase. Collectively, study provides deeper understanding DNAP-fork mechanism keeping active during stress.

Язык: Английский

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PrimPol-mediated repriming elicits gap-filling by template switching and promotes cellular tolerance to Cidofovir

DNA repair, Год журнала: 2024, Номер 145, С. 103787 - 103787

Опубликована: Ноя. 14, 2024

Язык: Английский

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