Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person Chk1 is a checkpoint kinase activated during genotoxic stres...
| Class:Id | Summation:176165 |
|---|---|
| _displayName | Chk1 is a checkpoint kinase activated during genotoxic stres... |
| _timestamp | 2006-03-11 18:36:01 |
| created | [InstanceEdit:176246] D'Eustachio, P, 2006-03-03 16:44:08 |
| literatureReference | [LiteratureReference:176337] ATR, Claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in the absence of DNA damage [LiteratureReference:176365] Human claspin is required for replication checkpoint control [LiteratureReference:176211] Rapid PIKK-Dependent Release of Chk1 from Chromatin Promotes the DNA-Damage Checkpoint Response [LiteratureReference:176143] Rapid activation of ATR by ionizing radiation requires ATM and Mre11 [LiteratureReference:176105] Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts [LiteratureReference:176217] Chk1, but not Chk2, inhibits Cdc25 phosphatases by a novel common mechanism [LiteratureReference:176342] Chk1 and Chk2 kinases in checkpoint control and cancer [LiteratureReference:176276] Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice [LiteratureReference:176206] Chk1 in the DNA damage response: conserved roles from yeasts to mammals |
| modified | [InstanceEdit:176809] D'Eustachio, P, 2006-03-11 18:35:59 |
| text | Chk1 is a checkpoint kinase activated during genotoxic stress. Like ATR, Chk1 is essential for viability in mammals. Targeted gene disruption in mice shows that loss of Chk1 causes peri-implantation embryonic lethality. Even though ATR-ATRIP not bound to ssDNA can phosphorylate Chk1, Chk1 activation is greatly enhanced when recruited to stalled replication forks by physical interaction with a modified form of claspin and the Rad9-Hus1-Rad1 sliding clamp. Activation of Chk1 occurs following phosphorylation of two sites (serine 317 and serine 345). Mutational analysis indicates that modification of both sites is essential for maximal kinase activity, while phosphorylation of only a single site causes only weak activation of Chk1. Following phosphorylation, Chk1 can diffuse away from the complex to further amplify the checkpoint signal. ATR appears to be the primary kinase activating Chk1 as conditions that activate ATR (ultraviolet irradiation or treatment with hydroxyurea) also activate Chk1. Stresses that activate ATM, e.g., ionizing irradiation, do not cause significant Chk1 activation. While the ATR and ATM pathways are distinct, there is interplay between the two. For example, double-strand DNA breaks can be processed in an ATM-dependent manner to generate structures that can cause ATR and hence Chk1 activation. The ATR and ATM pathways also have mechanistic similarities. Analogous to the Chk1 kinase existing downstream of ATR, the Chk2 checkpoint kinase is modified and activated by ATM. Although having distinct structures, Chk1 and Chk2 also have overlapping targets with some substrate sites phosphorylatable by both kinases (e.g., serine 20 of p53). |
| (summation) | [Reaction:176116] Recruitment and activation of Chk1 [Homo sapiens] |
| [Change default viewing format] | |
No pathways have been reviewed or authored by Chk1 is a checkpoint kinase activated during genotoxic stres... (176165)
