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13 - DNA Packaging for Information Retrieval and Propagation

from Part II - Design and operation of complex functions

Published online by Cambridge University Press:  06 August 2018

Michael Sheetz
Affiliation:
Columbia University, New York
Hanry Yu
Affiliation:
National University of Singapore
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Summary

If stretched out, the double-stranded DNA in a human cell nucleus would be almost 2 m in length. The complete DNA is packaged in a nucleus of 7–9 μm in diameter with histones and associated proteins. During the cell cycle, the DNA is available for transcription and replication, which will cause supercoiling and strand crossovers. In mammalian nuclei, the negatively charged DNA strands are first wound around a 6 nm, positively charged histone core. This forms a basic structure known as a nucleosome. Further compaction sees nucleosomes organized sometimes into 30 nm solenoids, which are subsequently condensed into looped chromatin structures. Dynamics in the solenoids allows DNA binding proteins to access the DNA strands on their surface. Despite the lack of observable nuclear movements in the light microscope, the nucleus is a hotbed of activity. For example, there is considerable evidence to indicate that DNA strands move through polymerizing enzymes and are scanned by other proteins. The nucleosomes are actively positioned by mechanoenzymes and although not fully understood, chromatin condensation at the core of chromosomes is known to be an energy-dependent process. In surface loop regions of chromatin, there is active transcription and recent studies indicate that chromatin is organized as flexible strings of uncondensed nucleosomes. Thus, inactive regions are hidden inside and active regions are on the outside of chromosomes.

Much More DNA than in Genes

The DNA sequence is often described as being the blueprint for the organism. However, this blueprint includes plans for self-repair and the mechanisms for avoiding damage from environmental challenges such as high temperature. As a result, there is considerable complexity in how the genetic information is propagated, as well as how the necessary portions are robustly read and transcribed. Some aspects of DNA structure and processing are understood, such as the checks that ensure only a single copy of the DNA is made in the S phase of the cell cycle. However, the roles of many features are not clear. For example, the majority of human DNA does not encode human genes that can be translated into proteins. Although normally silent, nearly 25% of the genome encodes for viruses that may be activated. In addition, there are large stretches of repetitive DNA sequences with no known purpose.

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