Figure 1.

IR-induced DNA damage response (DDR) pathways. DNA-PK and ATM preferentially activate the NHEJ and HR pathways, respectively. Both CHK1 and CHK2 phosphorylate cell division cycle 25 (CDC25) which influences the G1/S and G2/M checkpoints. WEE1 phosphorylates CDC25 which prevents progression into mitosis. Activation of p53 by the ATM-CHK2 cascade promotes p21 transcription, which arrests cells at G1/S phase or can stimulate apoptosis or cellular senescence. In terms of direct SSBs and those generated through intermediates of BER, PARP1 binds and promotes further repair through DNA polymerase β (POLβ) and X-ray repair cross-complementing 1 (XRCC1) in complex with DNA ligase IIIα. ATR is activated by stalled replication forks and through replication protein A (RPA) bound to single-stranded DNA.