Chromosomes and the cell cycle

CHROMOSOMES AND THE CELL CYCLE

The processes of DNA replication, cellular growth and cell division are strictly regulated to ensure that cells divide at period appropriate to cellular size and DNA status . A resting cell replicates its DNA during a diser synthetic period (S phase) once it has sufficient nutrients and cellular mass. A further cellular growth phase (G2) is required before the cell can divide into daughter cells. except in early embryonic divisions. As mitosis (M phase) commences, chromatin is remodelled to allow the chromosomes to condense; since they have replicated, they appear as a doublet structure of two daughter chromatids joined at the centromere. In the next stage, the nuclear envelope disassembles, and a new subcellular structure, the mitotic spindle, forms by the polymerisation of microtubules around Y-tubulin. Chromosomes attach to the spindle by their centromeres, and migrate to the centre of the spindle. A series of spindle motors then move the microtubules to opposite ends of the cell, carrying with them the centromeres which divide to ensure chromatid segregation. At the end of mitosis, nuclear membrane reforms around the two daughter cells chromosomes decondense, and a further period of cellular growth (G1) ensues.

The process of meiosis which generates the gametes is fundamentally different from mitosis in two respects. To ensure that after fertilisation a diploid (2n) cell is created, a second round of chromatid segregation occurs to reduce the DNA content of each gamete to haploid (n). Secondly, at the outset of meiosis, genetic material is exchanged between the paired chromosomes which form crossover structures known as chiasmata . Several chiasmata can be present per chromosomal pair. This process of DNA recombination is critical in generating the variation that enables species to adapt to their environment. Should such exchange of genetic material barely alter the DNA sequence on the resulting chromosomes-for example, in progeny derived from a single parental pair after generations of inbreeding the species risks extinction if exposed to environmental stresses, and is more likely to suffer from autosomal recessive diseases .

Normal mammalian cells are only able to undergo a finite number of cell divisions. Partial explanations of this phenomenon include failure to repair exogenous damage and defective processing of key macromolecules such as DNA. A further process appears to be of particular importance in limiting the general number of cell divisions, yet rendering specific cells capable of dividing an extended number of times, as required to generate a renewing stem cell, a germline cell and particularly cancerous cells. The ends of chromosomes, termed telomeres, are specialised structures that confer stability on the chromosome by coordinating and positioning chromosomes during mitosis, preventing aberrant chromosomal fusion events and enabling the cell to replicate chromosomal ends. Telomeres consist of a linear array of a Grich sequence, but the number of these repeats is reduced at each cell division since DNA polymerases cannot fully replicate blunt-ended DNA. Progressive shortening of the telomere is thought to be responsible for cellular senescence, though a relationship to the lifespan of an individual is not clear. Cells can counteract the loss of telomeric repeat units during cell division by adding them using the enzyme telomerase, and cells which express telomerase are able to undergo more divisions before becoming senescent.