Table 1.
Summary of DDR-associated genes, how they can be epigenetically regulated and their involvement in drug response.
Gene | Symbol | Summary | Reference Number |
---|---|---|---|
O6-Methylguanine-DNA Methyltransferase | MGMT | Methylated associated with increased sensitivity to temozolomide. Enhancer region associated with increased expression and resistance to temozolomide. | [1,3,5,6,26] |
Breast Cancer type 1 susceptibility protein | BRCA1 | Methylated associated with sensitivity to PARPi/platinum and loss of H3K27ac at enhancer regions. | [7,8,11,12,27,35] |
Breast Cancer type 2 susceptibility protein | BRCA2 | Deficiency causes chromatin conformation changes and increased sensitivity to PARPi/platinum. | [7,8,11,12,28] |
MutL Homolog 1 | MLH1 | Unmethylated associated with temozolomide/platinum resistance and loss of MMR. | [15,16,17,31] |
FA Complementation Group F | FANCF | Methylation associated with sensitivity to platinum, unmethylated associated with platinum resistance. | [24,25] |
FA Complementation Group A | FANCA | Germline mutation associated with increased sensitivity to DNA damaging agents. | [36] |
DNA Repair Protein RAD51 homolog 1 | RAD51 | High expression associated with platinum resistance. | [37] |
X-ray Repair Cross Complementing 2 | XRCC2 | Low expression associated with sensitivity to PARPi. | [38] |
X-ray Repair Cross Complementing 3 | XRCC3 | Low expression associated with sensitivity to PARPi. | [38] |
DNA Polymerase Delta 4 | POLD4 | Low expression associated with sensitivity to PARPi/platinum. | [39] |
RAD51 Paralog C | RAD51C | Reversion mutations associated with increased resistance to PARPi. | [52] |
RAD51 Paralog D | RAD51D | Reversion mutations associated with increased resistance to PARPi. | [52] |
Euchromatic Histone Lysine Methyltransferase 2 | EHMT2 | Maintains repressive H3K9 methylation marks. Recruits HR-associated factors, Inhibition of EHMT2 promotes DNA damage. | [58,59,63,64,66] |
Enhancer of Zeste Homolog 2 | EZH2 | Maintains repressive H3K27 methylation marks. Controls expression of multiple DDR-associated genes. Inhibition of EZH2 sensitises cells to PARPi. | [58,59,60,61,66] |