CELL DIVISION

Cell division and growth In unicellular organisms, cell division is the means of reproduction; in multicellular organisms, it is the means of tissue growth and maintenance. Survival of the higher organisms depends upon interactions between many cell types, and it is essential that a balanced distribution of types be maintained. This is achieved by the highly regulated process of cell proliferation. The growth and division of different cell populations are regulated in different ways, but the basic mechanisms are similar throughout multicellular organisms. Most tissues of the body grow by increasing their cell number, but this growth is highly regulated to maintain a balance between different tissues. In adults most cell division is involved in tissue renewal rather than growth, many types of cells undergoing continuous replacement. Skin cells, for example, are constantly being sloughed off and replaced; in this case the mature differentiated cells do not divide, but their population is renewed by division of immature stem cells. In certain other tissues, such as those of the liver, mature cells remain capable of division to allow growth or regeneration after injury. In contrast to these patterns, other classes of cell do not divide and are not renewable in the adult organism. These include heart muscle, nerve, and lens cells in mammals. Maintenance and repair of these cells is limited to replacing intracellular components rather than replacing entire cells. Duplication of the genetic material Before a cell can divide, it must accurately and completely duplicate the genetic information encoded in its DNA in order for its progeny cells to function and survive. This is a complex problem because of the great length of DNA molecules. Each human chromosome consists of a long double spiral, or helix, each strand of which consists of more than 100,000,000 nucleotides (see above The nucleus). The duplication of DNA is called DNA replication, and it is initiated by complex enzymes called DNA polymerases. These progress along the molecule, reading the sequences of nucleotides that are linked together to make DNA chains. Each strand of the DNA double helix, therefore, acts as a template specifying the nucleotide structure of a new growing chain. After replication, each of the two daughter DNA double helices consists of one parental DNA strand wound around one newly synthesized DNA strand. In order for DNA to replicate, the two strands must be unwound from each other. Enzymes called helicases unwind the two DNA strands, and additional proteins bind to the separated strands to stabilize them and prevent them from pairing again. In addition, a remarkable class of enzyme called DNA topoisomerase removes the helical twists by cutting either one or both strands and then resealing the cut. These enzymes can also untangle and unknot DNA when it is tightly coiled into a chromatin fibre. In the circular DNA of bacteria, replication starts at a unique site called the origin of replication, then proceeds in both directions around the molecule until the two processes meet, producing two daughter molecules. In rapidly growing bacteria, a second round of replication can start before the first has finished. The situation in higher organisms is more complicated, as replication moves more slowly than in bacteria. At 500 to 5,000 nucleotides per minute (versus 100,000 nucleotides per minute in bacteria), it would take a human chromosome about a month to replicate if started at a single site. Actually, replication begins at many sites on the long chromosomes of animals, plants, and fungi. Distances between adjacent initiation sites are not always the same; for example, they are closer in the rapidly dividing embryonic cells of frogs or flies than in adult cells of the same species. Less is known about the initiation sites of higher organisms than those of bacteria. Accurate DNA replication is crucial to ensure that daughter cells have exact copies of the genetic information for synthesizing proteins. Accuracy is achieved by a proofreading ability of the DNA polymerase itself. It can erase its own errors and then synthesize anew. There are also repair systems that correct genetic damage to DNA. For example, the incorporation of an incorrect nucleotide, or damage caused by mutagenic agents, can be corrected by cutting out a section of the daughter strand and recopying the parental strand.