PathwayStep4469 p53-Independent G1/S DNA damage checkpoint Pubmed10827953 Reactome Database ID Release 4369613 Reactome, http://www.reactome.org ReactomeREACT_1208 The G1 arrest induced by DNA damage has been ascribed to the transcription factor and tumor suppressor protein p53. To be effective within minutes after DNA damage, induction of the G1 block should exploit transcription and protein synthesis independent mechanisms.<p>Upon exposure to ultraviolet light (UV) or ionizing radiation (IR), the abundance and activity of a protein, Cdc25A, rapidly decreases; this DNA damage response is not dependent on p53. The rapid destruction of Cdc25A phosphatase prevents entry of a cell into S-phase, by maintaining the CyclinE:Cdk2 complexes in their T14Y15 phosphorylated form. p53-Independent DNA Damage Response