Histones: Dosage and Degradation
Rakesh Kumar Singh, Johanna Paik and Akash Gunjan
from: Epigenetics: A Reference Manual (Edited by: Jeffrey M. Craig and Nicholas C. Wong). Caister Academic Press, U.K. (2011)
In eukaryotes, the genetic material in the form of DNA is wrapped around histone proteins to form nucleoprotein filaments called chromatin. Histones help package the DNA to fit it inside the nucleus of each cell, which in turn regulates access to the genetic information contained within the DNA. Hence, all DNA transactions are likely to be affected by histone metabolism. Eukaryotes carry multiple histones genes that can potentially generate enormous quantities of histone proteins. When present in excess, the positively charged histones can potentially "stick" non-specifically to the negatively charged DNA and adversely affect processes that require access to DNA. Not surprisingly, aberrant histone stoichiometry, chromatin assembly or chromatin structure lead to genomic instability, which is characterized by the increased rate of acquisition of alterations in the genome and is associated with deleterious human conditions such as cancer and aging. Hence, histone synthesis is coupled to ongoing DNA replication and is regulated transcriptionally and posttranscriptionally. To further avoid the deleterious consequences of excess histones, a posttranslational regulatory mechanism was described recently whereby excess histones are targeted for degradation by the ubiquitin-proteasome system. In this chapter, we discuss the causes and consequences of excess histone accumulation, as well as the strategies that cells have evolved to deal with them read more ...