Research on the breast cancer chemotherapy targeting synthetic lethality caused by the factors in the DNA damage repair pathways.

本课题通过对DNA损伤修复通路的研究，将该通路中各因子引起的合成致死性应用于乳腺癌的治疗。我们发现，与同源DNA修复相关的基因启动子甲基化与化学敏感性有关。我们还发现PLK1的过表达通过抑制BRCA1的E3泛素连接酶活性导致细胞对CPT-11和PARP抑制剂的超敏反应，并且BARD1通过异染色质蛋白1 (HP1) γ与lys9 -二甲基化组蛋白H3相互作用以响应DNA损伤。

In this project we studied the DNA damage repair pathways to employ the synthetic lethality caused by the factors in the pathway for breast cancer therapy. We found that promoter methylation of genes implicating in the homology-directed DNA repair are associated with chemosensitivity. We also discovered that overexpression of PLK1 causes cellular hypersensitivity to CPT-11 and PARP inhibitor through suppression of the E3 ubiquitin ligase activity of BRCA1, and that BARD1 interacts with Lys9-dimethylated Histone H3 through heterochromatin protein 1 (HP1) gamma in response to DNA damage.