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• W3035036511 abstract "Abstract DNA2 is an essential nuclease–helicase implicated in DNA repair, lagging-strand DNA synthesis, and the recovery of stalled DNA replication forks (RFs). In Saccharomyces cerevisiae, dna2Δ inviability is reversed by deletion of the conserved helicase PIF1 and/or DNA damage checkpoint-mediator RAD9. It has been suggested that Pif1 drives the formation of long 5′-flaps during Okazaki fragment maturation, and that the essential function of Dna2 is to remove these intermediates. In the absence of Dna2, 5′-flaps are thought to accumulate on the lagging strand, resulting in DNA damage-checkpoint arrest and cell death. In line with Dna2’s role in RF recovery, we find that the loss of Dna2 results in severe chromosome under-replication downstream of endogenous and exogenous RF-stalling. Importantly, unfaithful chromosome replication in Dna2-mutant cells is exacerbated by Pif1, which triggers the DNA damage checkpoint along a pathway involving Pif1’s ability to promote homologous recombination-coupled replication. We propose that Dna2 fulfils its essential function by promoting RF recovery, facilitating replication completion while suppressing excessive RF restart by recombination-dependent replication (RDR) and checkpoint activation. The critical nature of Dna2’s role in controlling the fate of stalled RFs provides a framework to rationalize the involvement of DNA2 in Seckel syndrome and cancer." @default.
• W3035036511 created "2020-06-19" @default.
• W3035036511 creator A5016241358 @default.
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• W3035036511 date "2020-06-16" @default.
• W3035036511 modified "2023-10-03" @default.
• W3035036511 title "Disease-associated DNA2 nuclease–helicase protects cells from lethal chromosome under-replication" @default.
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• W3035036511 doi "https://doi.org/10.1093/nar/gkaa524" @default.
• W3035036511 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7367196" @default.
• W3035036511 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32544229" @default.
• W3035036511 hasPublicationYear "2020" @default.
• W3035036511 type Work @default.
• W3035036511 sameAs 3035036511 @default.

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