From: Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells
HDAC | Role in DNA damage/repair | Substrates involved in DNA damage response | References |
---|---|---|---|
Class I | Â | Â | Â |
HDAC1 | Protects from DNA damage, sustains DNA damage checkpoint, maintains DNA replication, regulates oxidative stress and NHEJ | H3K56, p21, p53, BRCA1, CHES1, PCNA, Top II, ATM, ATR, RFC, ING1a, APE1/Ref1 | |
HDAC2 | Participates in DNA damage signaling by translocation to nucleus; regulates DNA repair | H3K56, BRCA1, ATR | |
HDAC3 | Protects from DNA damage, maintains replication fork, mitotic spindle and helps in DNA repair and genomic stability via HDAC3/NCOR/SMRT complexes | H3K9/K14, H4K5/K12 | |
Class IIa | Â | Â | Â |
HDAC4 | Increases DNA repair by translocation to the nucleus and signaling repair | 53BP1 | |
HDAC9 | DNA repair through homologous recombination | Not yet identified | [43] |
Class IIb | Â | Â | Â |
HDAC6 | Role in chemosensitization | GADD153 | [80] |
HDAC10 | DNA repair through homologous recombination | Not yet identified | [43] |
Class III | Â | Â | Â |
SIRT1 | Protects from oxidative DNA damage, maintains telomere length and activates DNA repair through HR, NER, and BER | p53, FoXO1, WRN, Ku70, Tip60, APE1, H3K56, NBS1, MRN, telomere, XPA, XPC | |
SIRT3 | Transports to mitochondria and reduces oxidative DNA damage | Idh2, H4K16 | |
SIRT6 | Promotes DNA repair by HR, forms a complex with DNA-PK and resists DNA damage; maintains chromatin structure and genomic stability | H3K9/K56, CtIP, XPA, DNAPK |