Table 3.

Mechanisms of reactivation of Homologous Recombination repair.

Resistance Mechanism	Function
BRCA (or HR gene) reversion mutation	Restores open reading frame of gene, resulting in functional protein expression
Loss of BRCA1 promoter methylation	Restores BRCA1 function
Upregulated HSP90	Promotes BRCA-independent RAD51 loading onto damaged DNA
BRCA1 C-terminal domain mutation	Upregulation of BRCA1, in absence of BRCA1 reversion mutation
Loss 53BP1	Recruits Shieldin complex to inhibit DNA resection, initiating HR in a BRCA-independent manner.

Abbreviations; HR, Homologous Recombination; HSP90, Heat Shock Protein 90.