Bookmarking by histone methylation ensures chromosomal integrity during mitosis
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Online ISSN 1976-3786 Print ISSN 0253-6269
REVIEW
Bookmarking by histone methylation ensures chromosomal integrity during mitosis Ja-Eun Kim1
Received: 1 March 2019 / Accepted: 19 April 2019 Ó The Pharmaceutical Society of Korea 2019
Abstract The cell cycle is an orchestrated process that replicates DNA and transmits genetic information to daughter cells. Cell cycle progression is governed by diverse histone modifications that control gene transcription in a timely fashion. Histone modifications also regulate cell cycle progression by marking specific chromatic regions. While many reviews have covered histone phosphorylation and acetylation as regulators of the cell cycle, little attention has been paid to the roles of histone methylation in the faithful progression of mitosis. Indeed, specific histone methylations occurring before, during, or after mitosis affect kinetochore assembly and chromosome condensation and segregation. In addition to timing, histone methylations specify the chromatin regions such as chromosome arms, pericentromere, and centromere. Therefore, spatiotemporal programming of histone methylations ensures epigenetic inheritance through mitosis. This review mainly discusses histone methylations and their relevance to mitotic progression. Keywords Histone modification Histone methylation Epigenetics Cell cycle Mitosis Chromosomal stability
Introduction As mammalian cells grow and replicate, they pass through an ordered sequence of events called the cell cycle, which comprises several phases: G1-S-G2-M (Otto and Sicinski & Ja-Eun Kim [email protected] 1
Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
2017). Genomic DNA is replicated during the synthetic (S) phase, and chromosomes are segregated into two daughter cells during the mitotic (M) phase. G1 and G2 phase are gap phases to ensure that the cell is ready to proceed to the next steps: duplication and division of DNA, respectively. Mitosis itself comprises five phases: prophase, prometaphase, metaphase, anaphase, and telophase. The final step of cell division is cytokinesis, in which the cell cytoplasm divides. The fidelity of mitosis is critical to maintain identical genetic material in both daughter cells. Aberrant mitosis leads to mitotic arrest or death before the cell exits mitosis. Alternatively, mitotic slippage occurs when cells exit aberrant mitosis, which results in cell death, senescence or continued cycling with polyploidy. These events are referred to as mitotic catastrophe (Yamada and Gorbsky 2006). The cell cycle is tightly coordinated by numerous proteins (Harashima et al. 2013). Cyclin-dependent kinases (CDKs) complexed with cyclins act as major engines that push cells forward through the cell cycle phases; they do this by phosphorylating various protein substrates primarily involved in cell cycle progression. In addition, the functions of various genes and the signaling pathways also play a role in controlling the cell cycle. In particular, expression of cell
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