ArticleMolecular cell2009
The unstructured C-terminal tail of the 9-1-1 clamp subunit Ddc1 activates Mec1/ATR via two distinct mechanisms.
Article in Molecular cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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89 citing papers in PubMed, 133 citations in OpenAlex.
- An updated view on lagging strand DNA replication: implications for the replication stress response.Cell cycle (Georgetown, Tex.) · 2026Article
- Dpb11 facilitates the colocalization of Mec1-Ddc2 with its activators on gapped DNA.Cell reports · 2026Article
- Article
- The RPA-binding domain and the KKRK motif in Rad26ATRIP cooperate at the perturbed DNA replication fork for initiating checkpoint signalling.PLoS genetics · 2026Article
- Molecular interplay between the DNA damage checkpoint kinase Mec1-Ddc2 and its activator Dpb11 on gapped DNA.bioRxiv : the preprint server for biology · 2025Article
- Article
- The Potential for Targeting GCancers · 2024Review
- Prolonged Cell Cycle Arrest in Response to DNA damage in Yeast Requires the Maintenance of DNA Damage Signaling and the Spindle Assembly Checkpoint.bioRxiv : the preprint server for biology · 2024Article
- Multi-step control of homologous recombination via Mec1/ATR suppresses chromosomal rearrangements.The EMBO journal · 2024Article
- Yeast Rad52 is a homodecamer and possesses BRCA2-like bipartite Rad51 binding modes.Nature communications · 2023Article
- Homodecameric Rad52 promotes single-position Rad51 nucleation in homologous recombination.bioRxiv : the preprint server for biology · 2023Article
- Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast.PLoS genetics · 2023Article
- Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast.bioRxiv : the preprint server for biology · 2023Article
- Smc5/6 Complex Promotes Rad3Molecular and cellular biology · 2022Article
- The DNA damage checkpoint: A tale from budding yeast.Frontiers in genetics · 2022Review
- Phosphorylation-dependent assembly of DNA damage response systems and the central roles of TOPBP1.DNA repair · 2021Review
- Novel insights into the mechanism of cell cycle kinases Mec1(ATR) and Tel1(ATM).Critical reviews in biochemistry and molecular biology · 2021Article
- Dpb4 promotes resection of DNA double-strand breaks and checkpoint activation by acting in two different protein complexes.Nature communications · 2021Article
- Phosphoproteomics reveals a distinctive Mec1/ATR signaling response upon DNA end hyper-resection.The EMBO journal · 2021Article
- The secondary-structured DNA-binding activity of Dna2 endonuclease/helicase is critical to cell growth under replication stress.The FEBS journal · 2021Article
29 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
Funding
Abstract
DNA damage checkpoint pathways operate to prevent cell-cycle progression in response to DNA damage and replication stress. In S. cerevisiae, Mec1-Ddc2 (human ATR-ATRIP) is the principal checkpoint protein kinase. Biochemical studies have identified two factors, the 9-1-1 checkpoint clamp and the Dpb11/TopBP1 replication protein, as potential activators of Mec1/ATR. Here, we show that G1 phase checkpoint activation of Mec1 is achieved by the Ddc1 subunit of 9-1-1, while Dpb11 is dispensable. However, in G2, 9-1-1 activates Mec1 by two distinct mechanisms. One mechanism involves direct activation of Mec1 by Ddc1, while the second proceeds by Dpb11 recruitment mediated through Ddc1 T602 phosphorylation. Two aromatic residues, W352 and W544, localized to two widely separated, conserved motifs of Ddc1, are essential for Mec1 activation in vitro and checkpoint function in G1. Remarkably, small peptides that fuse the two tryptophan-containing motifs together are proficient in activating Mec1.
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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.