The genomic instability phenotype of BRCA1 and BRCA2 deficient cells provided an opportunity for PARP inhibitor treatment. Poly polymerase is involved in the repair of DNA single strand breaks, and failure of their repair can lead to the generation of DNA double strand breaks during DNA replication. Inhibition of PARP1 leads to a large increase in DSBs and to cell death in the absence of BRCA1 or 2 and/or in the absence of HR dependent DSB repair. This is the basis for the concept that PARP inhibitors induce synthetic lethality in HR repair deficient tumors and provides a novel strategy for cancer therapy, at least in breast cancer patients who have mutations in BRCA1 or BRCA2. Recent clinical trials of a PARP inhibitor reported a partial success in cancer therapy with less severe side (R,S)-Ivosidenib effects. Previously, we found that HP1 is an important factor for the activity of BRCA1 as part of the DNA damage response pathway. In this study, we investigated the expression level of Heterochromatin protein 1 in breast cancer cases. HP1 binds to dimethylated and buy Maytansinol trimethylated histone H3 and associates with heterochromatin in the nucleus. HP1 has diverse roles that include gene regulation and DNA damage response among others. We have recently shown that BRCA1 is not functional in its foci formation, homologous recombination repair, or G2/M checkpoint control in the absence of HP1 expression upon DSB induction. Since HP1 is an essential factor for BRCA1 function during the DNA damage response pathway, it is possible that HP1 expression levels may be altered during tumorigenesis. Here, we found the heterogeneous expression of all three HP1 subtypes in breast cancer patients. We uncovered that breast cancer patients with tumors expressing high levels of HP1 mRNA had less probability of survival. We also found the positive correlation of HP1 expression and Ki-67 cancer marker in breast cancer samples, suggesting potential significance of HP1 as a marker for breast cancer prognosis. Furthermore, we showed that PARP inhibitor ABT-888 was more effective in inducing death of HP1-deficient MCF7 breast cancer cells. These data suggest that HP1 level could not only serve as a useful marker for breast cancer prognosis but also as a predictive marker for PARP therapy. Previously, we reported that HP1 family is required for DNA damage response primarily through the regulation of BRCA1 function. HP1-depleted cells showed defective BRCA1 foci formation, homologous recombination DNA repair and G2/M cell cycle checkpoint control in response to irradiation. As this study showed that significant populations of breast cancer patients have low or no expression of at least one HP1 subtype, we tested the effect of individual HP1 on PARP inhibitor therapy. To achieve this goal, MCF7 ce
