Cell cycle and cell division WORLD OF MICROBIOLOGY AND IMMUNOLOGY104•
ligands. Examples of growth factors are as such: epidermal
growth factor (EGF), fibroblastic growth factor (FGF),
platelet-derived growth factor (PDGF), insulin-like growth
factor (IGF), or by hormones. PDGF and FGF act by regulat-
ing the phase G2 of the cell cycle and during mitosis. After
mitosis, they act again stimulating the daughter cells to grow,
thus leading them from G0 to G1. Therefore, FGF and PDGF
are also termed competence factors, whereas EGF and IGF are
termed progression factors, because they keep the process of
cellular progression to mitosis going on. Growth factors are
also classified (along with other molecules that promote the
cell cycle) as pro-mitotic signals. Hormones are also pro-
mitotic signals. For example, thyrotrophic hormone, one of the
hormones produced by the pituitary gland, induces the prolif-
eration of thyroid gland’s cells. Another pituitary hormone,
known as growth hormone or somatotrophic hormone (STH),
is responsible by body growth during childhood and early ado-
lescence, inducing the lengthening of the long bones and pro-
tein synthesis. Estrogens are hormones that do not occupy a
membrane receptor, but instead, penetrate the cell and the
nucleus, binding directly to specific sites in the DNA, thus
inducing the cell cycle.
Anti-mitotic signals may have several different origins,
such as cell-to-cell adhesion, factors of adhesion to the extra-
cellular matrix, or soluble factor such as TGF beta (tumor
growth factor beta), which inhibits abnormal cell proliferation,
proteins p53, p16, p21, APC, pRb, etc. These molecules are
the products of a class of genes called tumor suppressor genes.
Oncogenes, until recently also known as proto-oncogenes,
synthesize proteins that enhance the stimuli started by growth
factors, amplifying the mitotic signal to the nucleus, and/or
promoting the accomplishment of a necessary step of the cell
cycle. When each phase of the cell cycle is completed, the pro-teins involved in that phase are degraded, so that once the next
phase starts, the cell is unable to go back to the previous one.
Next to the end of phase G1, the cycle is paused by tumor sup-
pressor geneproducts, to allow verification and repair of
DNA damage. When DNA damage is not repairable, these
genes stimulate other intra-cellular pathways that induce the
cell into suicide or apoptosis (also known as programmed cell
death). To the end of phase G2, before the transition to mito-
sis, the cycle is paused again for a new verification and “deci-
sion”: either mitosis or apoptosis.
Along each pro-mitotic and anti-mitotic intra-cellular sig-
naling pathway, as well as along the apoptotic pathways, several
gene products (proteins and enzymes) are involved in an
orderly sequence of activation and inactivation, forming com-
plex webs of signal transmission and signal amplification to the
nucleus. The general goal of such cascades of signals is to
achieve the orderly progression of each phase of the cell cycle.
Mitosis always creates two completely identical cells
from the original cell. In mitosis, the total amount of DNA
doubles briefly, so that the subsequent daughter cells will ulti-
mately have the exact amount of DNA initially present in the
original cell. Mitosis is the process by which all of the cells of
the body divide and therefore reproduce. The only cells of the
body that do not duplicate through mitosis are the sex cells
(egg and sperm cells). These cells undergo a slightly different
type of cell division called meiosis, which allows each sex cell
produced to contain half of its original amount of DNA, in
anticipation of doubling it again when an egg and a sperm
unite during the course of conception.
Meiosis, also known as reduction division, consists of
two successive cell divisions in diploid cells. The two cell
divisions are similar to mitosis, but differ in that the chromo-
somes are duplicated only once, not twice. The result of meio-
sis is four haploid daughter cells. Because meiosis only occurs
in the sex organs (gonads), the daughter cells are the gametes
(spermatozoa or ova), which contain hereditary material. By
halving the number of chromosomes in the sex cells, meiosis
assures that the fusion of maternal and paternal gametes at fer-
tilization will result in offspring with the same chromosome
number as the parents. In other words, meiosis compensates
for chromosomes doubling at fertilization. The two successive
nuclear divisions are termed as meiosis I and meiosis II. Each
is further divided into four phases (prophase, metaphase,
anaphase, and telophase) with an intermediate phase (inter-
phase) preceding each nuclear division.
The events that take place during meiosis are similar in
many ways to the process of mitosis, in which one cell divides
to form two clones (exact copies) of itself. It is important to
note that the purpose and final products of mitosis and meio-
sis are very different.
Meiosis I is preceded by an interphase period in which
the DNA replicates (makes an exact duplicate of itself), result-
ing in two exact copies of each chromosome that are firmly
attached at one point, the centromere. Each copy is a sister
chromatid, and the pair are still considered as only one chro-
mosome. The first phase of meiosis I, prophase I, begins as the
chromosomes come together in homologous pairs in a process
known as synapsis. Homologous chromosomes, or homo-Segregation of eukaryotic genetic material during mitosis.womi_C 5/6/03 2:04 PM Page 104