ArticleMolecular cell2017
Checkpoint Kinase Rad53 Couples Leading- and Lagging-Strand DNA Synthesis under Replication Stress.
Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 67 citations in OpenAlex.
- Slx4 and Fun30/SMARCAD1 coordinate S-phase checkpoint regulation and replication fork protection in response to Top1-DNA crosslinks.Nucleic acids research · 2026Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Mechanistic models of asymmetric hand-over-hand translocation and nucleosome navigation by CMG helicase.Nature communications · 2025Article
- Stn1 supports Mec1 function in protecting stalled replication forks from degradation.PLoS genetics · 2025Article
- Leading and lagging strand abasic sites differentially affect vertebrate replisome progression but involve analogous bypass mechanisms.Nucleic acids research · 2025Article
- Eukaryotic Lagging Strand Synthesis is Distributive.bioRxiv : the preprint server for biology · 2025Article
- S-phase checkpoint protects from aberrant replication fork processing and degradation.Nucleic acids research · 2025Article
- The DNA replication checkpoint limits Okazaki fragment accumulation to protect and restart stalled forks.Molecular cell · 2025Article
- A tale of two strands: Decoding chromatin replication through strand-specific sequencing.Molecular cell · 2025Review
- Molecular mechanism of parental H3/H4 recycling at a replication fork.Nature communications · 2024Article
- Revised mechanism of hydroxyurea-induced cell cycle arrest and an improved alternative.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The PCNA-Pol δ complex couples lagging strand DNA synthesis to parental histone transfer for epigenetic inheritance.Science advances · 2024Article
- S-phase checkpoint prevents leading strand degradation from strand-associated nicks at stalled replication forks.Nucleic acids research · 2024Article
- The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork.International journal of molecular sciences · 2023Review
- The TIMELESS effort for timely DNA replication and protection.Cellular and molecular life sciences : CMLS · 2023Review
- Balancing act of a leading strand DNA polymerase-specific domain and its exonuclease domain promotes genome-wide sister replication fork symmetry.Genes & development · 2023Article
- Checkpoint kinase interaction with DNA polymerase alpha regulates replication progression during stress.Wellcome open research · 2023Article
- Rad53 arrests leading and lagging strand DNA synthesis via distinct mechanisms in response to DNA replication stress.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Mechanisms of theInternational journal of molecular sciences · 2022Review
- Yeast Stn1 promotes MCM to circumvent Rad53 control of the S phase checkpoint.Current genetics · 2022Article
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
The checkpoint kinase Rad53 is activated during replication stress to prevent fork collapse, an essential but poorly understood process. Here we show that Rad53 couples leading- and lagging-strand synthesis under replication stress. In rad53-1 cells stressed by dNTP depletion, the replicative DNA helicase, MCM, and the leading-strand DNA polymerase, Pol ε, move beyond the site of DNA synthesis, likely unwinding template DNA. Remarkably, DNA synthesis progresses further along the lagging strand than the leading strand, resulting in the exposure of long stretches of single-stranded leading-strand template. The asymmetric DNA synthesis in rad53-1 cells is suppressed by elevated levels of dNTPs in vivo, and the activity of Pol ε is compromised more than lagging-strand polymerase Pol δ at low dNTP concentrations in vitro. Therefore, we propose that Rad53 prevents the generation of excessive ssDNA under replication stress by coordinating DNA unwinding with synthesis of both strands.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.