**3.2. The regulation of TFs and nucleotide binding proteins by poly(ADP-ribosyl)ation**

PARP inhibitors, such as talazoparib, niraparib, rucaparib, olaparib, and veliparib, are clinically used for the treatment of cancer, especially when *BRCA1* and *BRCA2* gene mutations are present [89]. They all interact with the NAD+ -binding site of the catalytic domain of PARP1 and PARP2. A recent study indicated that the NAD+ -binding pocket of the PARP1 regulates interaction with DBC1, which is deleted in breast cancer 1, which is a known SIRT1 inhibitor protein [90]. A decrease in the NAD+ will upregulate the interaction between DBC1 and PARP1, leading to the suppression of its activity. This might partly explain why DNA repair declines with aging [91]. The poly(ADP-ribosyl)ation of proteins not only initiates the response to DNA damage, but also regulates the transcription of specific genes [92]. The poly(ADP-ribosyl)ation of C/EBPβ by PARP-1 modulates its transcriptional activity to enhance the expression of the genes encoding factors that regulate adipogenesis [93]. A recent study showed that the poly(ADP-ribosyl)ation of an RNA-binding protein HuR by PARP1 stabilizes *Cxcl2* gene transcripts [94]. Moreover, the poly(ADP-ribosyl)ation of FoxO3 suppresses its transcriptional activity and leads to cardiac hypertrophy [95]. Taken together, poly(ADP-ribosyl)ation, which consumes NAD+ as a substrate for PAR synthesis, may regulate transcription to respond to DNA damage-induced signals. Thus, it should be noted that PARP inhibitors not only limit the DNA damage response to lead to the death of cancerous cells, but also reduce the consumption of NAD+ molecules to modulate the transcription of specific genes.
