DNA damage induced G1-S checkpointÂÂÂ
| PAG Title | DNA damage induced G1-S checkpoint |
| PAG ID | WIG001818 |
| Type | P |
| Source Link |  Spike |
| Publication Reference | NA |
| PAG Description | DNA damage activates Ataxia telangiectasia mutated (ATM) and/or ATM and Rad3-related (ATR) signaling kinases, which trigger a dual wave of checkpoint responses in the G1-S boundary: (i) A quick (but transient) CDK2/1 inhibition achieved by (ATM-activated)-CHEK2 or (ATR-activated)-CHEK1 phosphorylation of the phosphatase CDC25A (the CDKs' activator), a phosphorylation that enhance the degradation of CDC25A. (ii) A Slower, but sustained process depends on the transcription factor TP53. ATM/ATR phosphorylates (directly or indirectly) both TP53 and MDM2 - the TP53 regulatory protein - which enhance TP53 stability and its DNA binding activity. TP53-mediated expression of p21(CDKN1A) leads to CycA-CDK2, CycE-CDK2, and CycB-CDC2 (CDK1) complexes inhibition, halting the cell in G1. |
| Species | Homo sapiens |
| nCoCo Score | 7,849 |
| Base PAG ID | WIG001818 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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