DNA damage DNA-damage-induced responses
DNA-damage-induced responses If the DNA damage is double-strand breaks (DSB) caused by ionizing radiation orradiomimetic agents, ataxia telangiectasia mutated serine-protein kinase ( ATM )is activated . If the DNA is damaged by UV light or UV-mimeticagents, ataxia telangiectasia and Rad3 related protein kinase ( ATR ) andDNA-activated protein kinase ( DNA-PK ) are activated . ATM,ATR and DNA-PK belong to phosphoinositide-3-kinases family. These stimulatedkinases signal the presence of DNA damage in mammalian cells by phosphorylating proteinsthat initiate cell-cycle arrest, apoptosis, and DNA repair , . There are three basic pathways, which participate in DNA-damages-induced cellresponse. Phosphorylation of the c ell cycle checkpoint kinase 2 ( Chk2 ) or c ell cyclecheckpoint kinase 1 ( Chk1 )  are the initial steps in the checkpoint arrest  and Brca1  participate in DNA-damage-induced cell cycleregulation (see maps 426. ATM/ATR regulation of G1/S checkpoint and 441.ATM/ATR regulation of G1/S checkpoint ). It is shown that DNA-damages-induced apoptosis is realized via the activatedp53, Brca1, c-Abl and Chk2 (see map 542 DNA-damages-inducedapoptosis ) , , . DNA repair is mediated mainly by Brca1  (see map 427. Roleof Brca1 and Brca2 in DNA Repair ).