Figure 3.

The role of bromodomain and extraterminal domain (BET) proteins in DNA damage response (DDR). DNA double-stranded breaks (DSB) are recognized by the MRN complex (NBS1, MRE11 and RAD51) and ATM/ATR kinases, followed by H2AX phosphorylation and activation of CHK1/CHK2 kinases, leading to diverse cellular responses, including cell cycle arrest and DNA repair. DSBs are mainly repaired through homologous recombination (HR), a multistep process encompassing DNA damage recognition, DNA end resection, strand invasion, repair synthesis and end ligation. BET controls key HR proteins’ transcription: BRCA1, RAD51 and CtIP, through interaction with their promoter regions. BRCA1,BRCA2, BRIP1, CtIP, FANCD2, CHK1, CHK2, MRE11, RAD50, RAD51, TIP60 and WEE1 expression is sensitive to BET inhibitors (BETis).