If the DNA damage is double-strand breaks (DSB) caused by ionizing radiation or radiomimetic agents, ataxia telangiectasia mutated serine-protein kinase ( ATM ) is activated . If the DNA is damaged by UV light or UV-mimetic agents, ataxia telangiectasia and Rad3 related protein kinase ( ATR ) and DNA-activated protein kinase ( DNA-PK ) are activated . ATM, ATR and DNA-PK belong to phosphoinositide-3-kinases family. These stimulated kinases signal the presence of DNA damage in mammalian cells by phosphorylating proteins that initiate cell-cycle arrest, apoptosis, and DNA repair , . There are three basic pathways, which participate in DNA-damages-induced cell response.
Phosphorylation of the cell cycle checkpoint kinase 2 ( Chk2 ) or cell cycle checkpoint kinase 1 ( Chk1 )  by ATM and/or ATR  are the initial steps in the checkpoint arrest . Phosphorylated by phosphoinositide-3-kinases directly or indirectly, p53  and Brca1  participate in DNA-damage-induced cell cycle regulation (see maps 426. ATM/ATR regulation of G1/S checkpoint and 441. ATM/ATR regulation of G1/S checkpoint ).
DNA repair is mediated mainly by Brca1  (see map 427. Role of Brca1 and Brca2 in DNA Repair ).