Fitieh Amira, Locke Andrew J, Motamedi Mobina, Ismail Ismail Hassan
Biophysics Department, Faculty of Science, Cairo University, Giza 12613, Egypt.
Division of Experimental Oncology, Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada.
Int J Mol Sci. 2021 Mar 15;22(6):2976. doi: 10.3390/ijms22062976.
The polycomb group (PcG) proteins are a class of transcriptional repressors that mediate gene silencing through histone post-translational modifications. They are involved in the maintenance of stem cell self-renewal and proliferation, processes that are often dysregulated in cancer. Apart from their canonical functions in epigenetic gene silencing, several studies have uncovered a function for PcG proteins in DNA damage signaling and repair. In particular, members of the poly-comb group complexes (PRC) 1 and 2 have been shown to recruit to sites of DNA damage and mediate DNA double-strand break repair. Here, we review current understanding of the PRCs and their roles in cancer development. We then focus on the PRC1 member BMI1, discussing the current state of knowledge of its role in DNA repair and genome integrity, and outline how it can be targeted pharmacologically.
多梳蛋白家族（PcG）是一类转录抑制因子，通过组蛋白翻译后修饰介导基因沉默。它们参与干细胞自我更新和增殖的维持，而这些过程在癌症中常常失调。除了在表观遗传基因沉默中的经典功能外，多项研究还揭示了PcG蛋白在DNA损伤信号传导和修复中的作用。特别是，多梳蛋白家族复合体（PRC）1和2的成员已被证明可募集到DNA损伤位点并介导DNA双链断裂修复。在此，我们综述了目前对PRC及其在癌症发展中作用的理解。然后我们聚焦于PRC1成员BMI1，讨论其在DNA修复和基因组完整性方面作用的当前知识状态，并概述如何从药理学角度对其进行靶向治疗。
