The silent guardian: unraveling the roles of H3K9me3 in genome maintenance

Abstract

Genomic integrity is a fundamental prerequisite for all living organisms, ensuring the accurate transmission of genetic information and stability of cellular functions across generations. The maintenance of genome integrity relies on a meticulously orchestrated network encompassing a variety of DNA repair factors and pathways. In eukaryotic cells, genomic DNA is assembled into chromatin, a highly organized complex of proteins and DNA. Therefore, chromatin and epigenetic factors have emerged as crucial guardians against genotoxic stress. In this review, we provide a comprehensive summary of the multifaceted roles of H3K9me3, a histone mark associated with silent chromatin, in DNA damage repair and genome maintenance, elucidating its dynamic participation in chromatin organization, silencing of repetitive DNA sequences, and modulation of DNA repair pathways. Importantly, we discuss the potential contribution of H3K9me3 to epigenetic memory following DNA damage, which introduces an additional layer of complexity to our comprehension of genomic surveillance. Finally, we explore the implications of H3K9me3 dysregulation in human cancers and the promising therapeutic avenues that may arise from a nuanced understanding of its function in maintaining genomic stability.

Keywords

H3K9me3 / DNA repair / Genome stability / Repetitive DNA / DNA replication / Epigenetic memory

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Funding

National Institute of General Medical Sciences(R35GM118015)