Chromosome structures

Abstract

Chromosomes are large subcellular structures, visible in the light microscope, that are found in the nuclei of most eukaryotic cells. Each chromosome consists of a single very long DNA molecule that has been compacted approximately 10,000-fold by interactions with proteins, such that the resulting chromosome structure fits within a typical eukaryotic nucleus of only 10 microns in diameter. Several levels of structural organisation are involved in the formation of chromosomes. Most chromosomal DNA is wrapped in left-handed superhelical turns around protein 'spools', called histone octamers, to form nucleosomes. Arrays of these nucleosomes, or 'beads on a string', are further compacted into solenoidal structures, called 30 nm chromatin fibres. The chromatin fibres are, in turn, compacted approximately 250-fold to form topologically independent 'looped' DNA domains, each loop containing about 20,000-100,000 nucleotide pairs of DNA extending from a proteinaceous central scaffold. Some chromosomes, such as lampbrush and polytene chromosomes, can be seen in certain specialised cells during interphase. Metaphase chromosomes, which can be stained to reveal characteristic banding patterns, are formed in most eukaryotic cells during mitosis. Formation of chromosome structures and the nuclei that envelop them involves discrete steps of nucleosome assembly, scaffold assembly, and nuclear envelope assembly, and can be carried out in cell-free extracts of animal eggs. Centromeres, the regions that mediate attachment of a chromosome to a meiotic or mitotic spindle, and telomeres, the natural ends of chromosomes, are structures that ensure that the correct number of full length chromosomes are maintained during the cell cycle. Most chromosome structures (nucleosomes, chromatin fibres, and scaffold loop domains) form from virtually any DNA sequence, but centromeres and telomeres are both composed of specific DNA sequences complexed with specific binding proteins. Recently, complete DNA sequences of entire chromosomes have been determined, and our rapidly emerging knowledge of chromosome structures is beginning to provide insights into the molecular basis of human disease.