The Role of Polycomb Group Protein BMI1 in DNA Repair and Genomic Stability

被引:18
|
作者
Fitieh, Amira [1 ,2 ]
Locke, Andrew J. [2 ]
Motamedi, Mobina [2 ]
Ismail, Ismail Hassan [1 ,2 ]
机构
[1] Cairo Univ, Fac Sci, Biophys Dept, Giza 12613, Egypt
[2] Univ Alberta, Fac Med & Dent, Dept Oncol, Div Expt Oncol, 11560 Univ Ave, Edmonton, AB T6G 1Z2, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
chromatin; genome instability; histone modification; transcription silencing; DNA repair; PcG; polycomb; PRC1; PRC2; BMI1; EZH2; HISTONE METHYLTRANSFERASE ACTIVITY; CPG ISLAND HYPERMETHYLATION; AGGRESSIVE BREAST-CANCER; TUMOR-SUPPRESSOR GENES; CELL SELF-RENEWAL; DAMAGE RESPONSE; INCREASED EXPRESSION; STEM-CELLS; DEVELOPMENTAL REGULATORS; HOMOLOGOUS RECOMBINATION;
D O I
10.3390/ijms22062976
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1 / 23
页数:23
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