Chapter 4The Transmission of DNA at Cell Division

DNA ReplicationCell DivisionMitosis 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 acoordinated 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 continoussynthesis on the leading strand anddiscontinous synthesis on the lagging strand.

All DNA polymerases synthezise only in the 5'to 3' direction.

Meselson and Stahl (1958!) showed that DNA replicatessemiconservatively. They used the heavy isotope of nitrogen (15N) tolabel 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 Okazakifragment. A complex containing helicase and 2 DNA polymerases carries out the coordinatedsynthesis of both strands. The two polymerases are attached to each other and move withthe 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 producestwo 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 forDNA replication. If a primingsite was located at the end of achromosome, this DNA segmentwould remain unreplicated afterthe primer is degraded andwould not be available during thenext round of DNA replication.

Telomeres protect the ends of chromosomes

Telomerasescontain specific RNA molecules that are part of the enzymecomplex and serve as complementary templates for the telomericrepeat unit. Telomerase is a type of reverse transcriptase.

Telomere lenght can varyduring development

Vizualization of telomeres

The chromosomes haveformed sister chromatides.An unbroken nucleus is shownat 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 DNAmolecules become bound to histone proteins. At this stage two chromosomes consists oftwo sister chromatides, each of which contains one of the replicated DNA molecules.The two sister chromatides are always identical.

DNA and gene transmissionduring asexual and sexual celldivisions in eukaryotes.S phase and the main stagesof mitosis and meiosis areshown. The diagramsemphasize the DNA contentof each cell and chromosome.The first two panels in eachcolumn show DNA replication,which occurs during the Sphase; the remaining panelsshow mitosis or meiosis. Thealleles A and a of one geneare used to show howgenotypes are transmittedduring cell division.

The stages of mitosis

The stages of meiosis

The process of meiosisstarts with diploidmeiocytes in thereproductive tissue andproduces an array ofhaploid cells withdiverse genotypes.

Just before the first nuclear division, homologous chromosomes pair along theirlengths, so that now for each chromosomal type there are two pairs of sisterchromatids juxtaposed, making a bundle of four also called a tetrad. At thetetrad stage a remarkable process occurs: paired nonsister chromatidsexchange homologous sections of DNA through breakage and reunion of theirarms at points called crossovers.

Sexual cell division and crossover