ArticleGenes & development2018
Separable roles for Mec1/ATR in genome maintenance, DNA replication, and checkpoint signaling.
Article in Genes & development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- An updated view on lagging strand DNA replication: implications for the replication stress response.Cell cycle (Georgetown, Tex.) · 2026Article
- Slx4 and Fun30/SMARCAD1 coordinate S-phase checkpoint regulation and replication fork protection in response to Top1-DNA crosslinks.Nucleic acids research · 2026Article
- DNA polymerase α/primase extraction from chromatin by VCP/p97 restricts ATR activation during unperturbed DNA replication.Nature communications · 2025Article
- DNA Damage and Replication Stress Checkpoints.Annual review of biochemistry · 2025Review
- Control of Replication Stress Response by Cytosolic Fe-S Cluster Assembly (CIA) Machinery.Cells · 2025Review
- Mms22-Rtt107 axis attenuates the DNA damage checkpoint and the stability of the Rad9 checkpoint mediator.Nature communications · 2025Article
- Investigating Fission Yeast Mutagenesis Using Canavanine Sensitivity Assays.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Emerin preserves stem cell survival through maintenance of centrosome and nuclear lamina structure.Development (Cambridge, England) · 2024Article
- Profiling Tel1 Signaling Reveals a Non-Canonical Motif Targeting DNA Repair and Telomere Control Machineries.bioRxiv : the preprint server for biology · 2024Article
- Multi-step control of homologous recombination via Mec1/ATR suppresses chromosomal rearrangements.The EMBO journal · 2024Article
- The Mms22-Rtt107 axis dampens the DNA damage checkpoint by reducing the stability of the Rad9 checkpoint mediator.Research square · 2024Article
- Starting DNA Synthesis: Initiation Processes during the Replication of Chromosomal DNA in Humans.Genes · 2024Review
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- Review
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- A regulatory phosphorylation site on Mec1 controls chromatin occupancy of RNA polymerases during replication stress.The EMBO journal · 2021Article
- Novel insights into the mechanism of cell cycle kinases Mec1(ATR) and Tel1(ATM).Critical reviews in biochemistry and molecular biology · 2021Article
- Fe-NTA Microcolumn Purification of Phosphopeptides from Immunoprecipitation (IP) Eluates for Mass Spectrometry Analysis.Bio-protocol · 2021Article
- Checkpoint-mediated DNA polymerase ε exonuclease activity curbing counteracts resection-driven fork collapse.Molecular cell · 2021Article
- Phosphoproteomics reveals a distinctive Mec1/ATR signaling response upon DNA end hyper-resection.The EMBO journal · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The Mec1/ATR kinase coordinates multiple cellular responses to replication stress. In addition to its canonical role in activating the checkpoint kinase Rad53, Mec1 also plays checkpoint-independent roles in genome maintenance that are not well understood. Here we used a combined genetic-phosphoproteomic approach to manipulate Mec1 activation and globally monitor Mec1 signaling, allowing us to delineate distinct checkpoint-independent modes of Mec1 action. Using cells in which endogenous Mec1 activators were genetically ablated, we found that expression of "free" Mec1 activation domains (MADs) can robustly activate Mec1 and rescue the severe DNA replication and growth defects of these cells back to wild-type levels. However, unlike the activation mediated by endogenous activator proteins, "free" MADs are unable to stimulate Mec1-mediated suppression of gross chromosomal rearrangements (GCRs), revealing that Mec1's role in genome maintenance is separable from a previously unappreciated proreplicative function. Both Mec1's functions in promoting replication and suppressing GCRs are independent of the downstream checkpoint kinases. Additionally, Mec1-dependent GCR suppression seems to require localized Mec1 action at DNA lesions, which correlates with the phosphorylation of activator-proximal substrates involved in homologous recombination-mediated DNA repair. These findings establish that Mec1 initiates checkpoint signaling, promotes DNA replication, and maintains genetic stability through distinct modes of action.
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Registered trials
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.