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. 2018 Jul 30;9:415. doi: 10.3389/fendo.2018.00415

Figure 2.

Figure 2

A simplified diagram of the DDR network adapted from Furgason and Bahassi (94). When genomic DNA is faced with various DNA damages, such as but not limited to DSBs, DNA crosslinking damage or alkylation damage, sensor proteins such as γH2AX and the MRE11/RAD50/NBS1 (MRN) complex will then recruit and activate the PIKK kinases, including ATM, ATR and DNA-PK. These PIKK kinases will then phosphorylate downstream targets, including scaffold proteins, regulatory proteins and downstream kinases. Upon activation, these proteins will subsequently phosphorylate effector proteins to undergo cell cycle arrest, DNA repair or apoptosis. For a detailed mechanistic analysis of the DDR, please refer to Ciccia and Elledge (92).