Chromatin Assembly from Yeast to Man: Conserved Factors and Conserved Molecular Mechanisms

Troy   A.A.   Harkness

Abstract

The maintenance and assembly of chromatin is critical for the health of all cells. Cells, whether dividing or quiescent, that propagate damaged DNA or maintain chromosomes that are not properly assembled and/or packaged will ultimately succumb to genomic instability and cell death. Chromatin, the building block of the chromosome, is composed of repeated units of 147 basepairs of DNA wrapped around two copies of each of the four core histones, H2A, H2B, H3 and H4. Histones within chromatin serve as templates for a host of posttranslational modifications that facilitate virtually all events that require chromatin or chromosomes. Many studies have focused on the molecular mechanisms mediating and regulating the assembly process. These studies have utilized model systems ranging from yeast to humans. The regulatory processes are tightly linked to the cell cycle and require precise interactions between kinase cascades and the ubiquitintargeting pathway. It appears likely that not only are the series of factors required to assemble chromatin conserved across evolutionary boundaries, but so are the regulatory mechanisms that control these processes. The implications of these findings to research make it clear that lower eukaryotic model systems provide a powerful opportunity to learn valuable lessons about complicated higher eukaryotic molecular pathways. The lessons learned from yeast studies will provide valuable insight into understanding the disease processes that occur in humans as a result of impaired chromatin assembly.

Keywords: chromatin assembly, caf-I, anaphase promoting complex, mitosis, evolutionary conservation

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