KAT6A Condensates Impair PARP1 Trapping of PARP Inhibitors in Ovarian Cancer
Zhiyan Zhan,
Jiarong Zhang,
Huisheng Liang
et al.
Abstract:Most clinical PARP inhibitors (PARPis) trap PARP1 in a chromatin‐bound state, leading to PARPi‐mediated cytotoxicity. PARPi resistance impedes the treatment of ovarian cancer in clinical practice. However, the mechanism by which cancer cells overcome PARP1 trapping to develop PARPi resistance remains unclear. Here, it is shown that high levels of KAT6A promote PARPi resistance in ovarian cancer, regardless of its catalytic activity. Mechanistically, the liquid‐liquid phase separation (LLPS) of KAT6A, facilitat… Show more
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