14.4 The Cell Cycle

191

gene from which the copy was made. The basis for McClintock’s proposal was her

observation of rapid variation of the colours of maize kernels from one generation

to another; the interpretation of these changes was that a gene coding for colour

could be inactivated if a transposon were inserted within it, but the transposon could,

with equal facility, be removed during the next round of meiosis, resulting in the

reappearance of the colour.

14.4.4

The Structure of the Chromosome

DNA is subject to oxidation, hydrolysis, alkylation, strand breaks, and so forth,

countered by various repair mechanisms as discussed in Sect. 14.7.2. Molecular

machinery (called “SOS”) is available to allow replication to proceed despite lesions.

Mistakes are the origin of the genotypic mutations leading to the phenotypic variety

required by Darwin’s theory (see Sect. 4.1).

Eukaryotic DNA is organized into chromatin, a protein–DNA complex. The

fundamental unit of chromatin structure is the nucleosome, ³³ a spheroidal complex

about 9 nm in diameter made by eight proteins called histones, around which a stretch

of 140–200 DNA base pairs is wrapped (recall that the DNA double helix is about

2 nm in diameter). The chromosome is constituted from successive nucleosomes,

joined by short stretches of so-called linker (non-nucleosomal) DNA. The string

of nucleosomes and their linkers are then compacted into fibres about 30 nm in

diameter, and these in turn are compactly folded to form the so-called chromatin

loops, about 300 nm in diameter, of the chromosome. Much of the DNA, perhaps

as much as 90% in a resting cell, is in this highly condensed, somewhat inert state

called heterochromatin. The condensation appears to occur in association with long

sequences of repetitive DNA. Hypermethylation of cytosine is typical (see Sect.

14.8.4). The active portion, available for transcription, is known as euchromatin.

The protein core of the nucleosome plays a highly significant rôle in the regula-

tion of transcription (Sect. 14.8.2). The amino acids of the histones are subject to

many modifications, such as a acetylation, methylation, phosphorylation, and ubiqui-

tination. Hypoacetylation of lysine is associated with heterochromatin formation. ³⁴

Methylation of specific lysines is also associated with heterochromatin (and silenc-

ing of euchromatin genes). It is important to bear in mind that histone modification

is a highly dynamic process, constantly under adjustment. Furthermore, there is evi-

dence that the histones are precisely positioned relative to the DNA according to its

sequence. ³⁵

33 Richmond and Davey (2003).

34 See, for example, Jenuwein and Allis (2001) and Richards and Elgin (2002).

35 Audit et al. (2002).