ArticleThe Journal of biological chemistry2009
ATRMec1 phosphorylation-independent activation of Chk1 in vivo.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- A C-degron regulates Chk1 kinase by allowing stability of inactive Chk1 and by making it short- lived upon activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Article
- Conformational Change of Human Checkpoint Kinase 1 (Chk1) Induced by DNA Damage.The Journal of biological chemistry · 2016Article
- KA1-targeted regulatory domain mutations activate Chk1 in the absence of DNA damage.Scientific reports · 2015Article
- Site-specific phosphorylation of the DNA damage response mediator rad9 by cyclin-dependent kinases regulates activation of checkpoint kinase 1.PLoS genetics · 2013Article
- Regulatory motifs in Chk1.Cell cycle (Georgetown, Tex.) · 2013Article
- CRL4(CDT2) targets CHK1 for PCNA-independent destruction.Molecular and cellular biology · 2013Article
- Autoregulatory mechanisms of phosphorylation of checkpoint kinase 1.Cancer research · 2012Article
- Phosphorylation-dependent interactions between Crb2 and Chk1 are essential for DNA damage checkpoint.PLoS genetics · 2012Article
- Eukaryotic DNA damage checkpoint activation in response to double-strand breaks.Cellular and molecular life sciences : CMLS · 2012Review
- Targeting the checkpoint kinase Chk1 in cancer therapy.Cell cycle (Georgetown, Tex.) · 2010Review
- Conserved ATRMec1 phosphorylation-independent activation of Chk1 by single amino acid substitution in the GD domain.Cell cycle (Georgetown, Tex.) · 2009Article
- The Multifaceted Role of Rad9 in the DNA Damage Response of Saccharomyces cerevisiae.Yeast (Chichester, England)Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The conserved protein kinase Chk1 is a player in the defense against DNA damage and replication blocks. The current model is that after DNA damage or replication blocks, ATR(Mec1) phosphorylates Chk1 on the non-catalytic C-terminal domain. However, the mechanism of activation of Chk1 and the function of the Chk1 C terminus in vivo remains largely unknown. In this study we used an in vivo assay to examine the role of the C terminus of Chk1 in the response to DNA damage and replication blocks. The conserved ATR(Mec1) phosphorylation sites were essential for the checkpoint response to DNA damage and replication blocks in vivo; that is, that mutation of the sites caused lethality when DNA replication was stalled by hydroxyurea. Despite this, loss of the ATR(Mec1) phosphorylation sites did not change the kinase activity of Chk1 in vitro. Furthermore, a single amino acid substitution at an invariant leucine in a conserved domain of the non-catalytic C terminus restored viability to cells expressing the ATR(Mec1) phosphorylation site-mutated protein and relieved the requirement of an upstream mediator for Chk1 activation. Our findings show that a single amino acid substitution in the C terminus, which could lead to an allosteric change in Chk1, allows it to bypass the requirement of the conserved ATR(Mec1) phosphorylation sites for checkpoint function.
Indexed as
Identifiers
What OpenQuestion holds
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.