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Chapter 4
The Transmission of DNA at Cell Division
DNA Replication
Cell Division
Mitosis
Meiosis
The faithful transmission of genotype at cell division,
illustrated by the behaviour of tumor cells
Cell division, nuclear division, chromosome division, and DNA replication occur in a
coordinated manner, producing daugther cells with identical genetic material.
DNA Replication
• DNA replication is prerequisite to cell division.
• DNA is replicated by using each strand as template for
synthesis of the complementary strand.
– one strand is synthesized continuously, the other
discontinuously
– all nucleotides are added at the 3’ end of the growing
strand
• Replicated chromosomes are partitioned to nuclei of
daughter cells in mitosis.
• Meiosis distributes replicated chromosomes to haploid
daughter cells in two nuclear and cell divisions.
A DNA replication fork, nucleotides are added to the 3' ends
DNA Replication
is semiconservative and semidiscontionous.
DNA synthesis proceeds by continous
synthesis on the leading strand and
discontinous synthesis on the lagging strand.
All DNA polymerases synthezise only in the 5'
to 3' direction.
Meselson and Stahl (1958!) showed that DNA replicates
semiconservatively. They used the heavy isotope of nitrogen (15N) to
label DNA of E. coli.
Replication fork
Lagging strand synthesis
Replication for at the beginning (a) and at the end (b) of the synthesis of an Okazaki
fragment. A complex containing helicase and 2 DNA polymerases carries out the coordinated
synthesis of both strands. The two polymerases are attached to each other and move with
the replication fork.
The fidelity of DNA polymerization is very high, one error per 109 bases
(proofreading!).
DNA replication initiates at specific sites called origins of replication. Each origin produces
two replication forks that move bidirectionally in opposite directions.
Replication of circular DNA:
generation of θ (theta)
structures
Replication of circular DNA:
the rolling circle model
Replication of linear DNA: the problem at the ends
RNA primers are required for
DNA replication. If a priming
site was located at the end of a
chromosome, this DNA segment
would remain unreplicated after
the primer is degraded and
would not be available during the
next round of DNA replication.
Telomeres protect the ends of chromosomes
Telomerases
contain specific RNA molecules that are part of the enzyme
complex and serve as complementary templates for the telomeric
repeat unit. Telomerase is a type of reverse transcriptase.
Telomere lenght can vary
during development
Vizualization of telomeres
The chromosomes have
formed sister chromatides.
An unbroken nucleus is shown
at the bottom.
Cell division
• Asexual cell division
• Sexual cell division
Cell cycle
-
G1: gap (growth)
S: DNA replication, forms
sister chromatids
G2: gap (growth)
M: mitosis (nuclear division)
and cytokinesis
The life cycle of humans (animals)
The life cycle of plants
Mus musculus has 25.000 genes and is the model closest to humans.
The plant model Arabidopsis thaliana has 25.000 genes.
The life cycle of fungi
During S phase the DNA of each chromosome is replicated. Both daughter DNA
molecules become bound to histone proteins. At this stage two chromosomes consists of
two sister chromatides, each of which contains one of the replicated DNA molecules.
The two sister chromatides are always identical.
DNA and gene transmission
during asexual and sexual cell
divisions in eukaryotes.
S phase and the main stages
of mitosis and meiosis are
shown. The diagrams
emphasize the DNA content
of each cell and chromosome.
The first two panels in each
column show DNA replication,
which occurs during the S
phase; the remaining panels
show mitosis or meiosis. The
alleles A and a of one gene
are used to show how
genotypes are transmitted
during cell division.
The stages of mitosis
The stages of meiosis
The process of meiosis
starts with diploid
meiocytes in the
reproductive tissue and
produces an array of
haploid cells with
diverse genotypes.
Sexual cell division and crossover
Just before the first nuclear division, homologous chromosomes pair along their
lengths, so that now for each chromosomal type there are two pairs of sister
chromatids juxtaposed, making a bundle of four also called a tetrad. At the
tetrad stage a remarkable process occurs: paired nonsister chromatids
exchange homologous sections of DNA through breakage and reunion of their
arms at points called crossovers.