<P> When DNA damage occurs , or when the cell detects any defects which necessitate it to delay or halt the cell cycle in G1 , arrest occurs through several mechanisms . The rapid response involves phosphorylation events that initiate with either kinase ATM ( Ataxia telangiectasia mutated ) or ATR ( Ataxia Telangiectasia and Rad3 related ) , which act as sensors , depending on the type of damage . These kinases phosphorylate and activate the effector kinases Chk2 and Chk1 , respectively , which in turn phosphorylate the phosphatase Cdc25A , thus marking it for ubiquitination and degradation . As Cdc25A activates the previously mentioned cyclin E-CDK2 complex by removing inhibitory phosphates from CDK2 , in the absence of Cdc25A , cyclin E-CDK2 remains inactive , and the cell remains in G1 . To maintain the arrest , another response is initiated , by which Chk2 or Chk1 phosphorylate p53 , a tumor suppressor , and this stabilizes p53 by preventing it from binding Mdm2 , a ubiquitin ligase which inhibits p53 by targeting it for degradation . The stable p53 then acts a transcriptional activator of several target genes , including p21 , an inhibitor of the G1 - to - S promoting complex cyclin E-CDK21 . In addition , another mechanism by which p21 is activated is through the accumulation of p16 in response to DNA damage . p16 disrupts cyclin D - CDK4 complexes , thus causing the release of p21 from the complexes , which leads to the dephosphorylation and activation of Rb , which allows Rb to bind and inhibit E2F1 - 3 , thus keeping the cell from transitioning to S phase . Recently , some aspects of this model have been disputed . </P>
which molecule initiates the halt of the cycle when damaged dna is detected in g1
Cdc25A