CELL CYCLE CELL CYCLE

AND CELL DIVISIONAND CELL DIVISION

Prokaryotic and eukaryotic cells differ markedly in Prokaryotic and eukaryotic cells differ markedly in the way they coordinate DNA synthesis and in the the way they coordinate DNA synthesis and in the subsequent equal partitioning of DNA during cell subsequent equal partitioning of DNA during cell division:division:

Prokaryotes:Prokaryotes: - no specialized structure for division is visible- no specialized structure for division is visible- DNA replication is followed immediately - DNA replication is followed immediately by cell divisionby cell division

Eukaryotes:Eukaryotes: - DNA synthesis and cell division occur in- DNA synthesis and cell division occur in

special phases of the cell cyclespecial phases of the cell cycle

Phases of the cell cycle:Phases of the cell cycle:

Cellular processes involving nucleic acids

Gene expression

Cell d

iv ision

DNA

DNA

RNA ProteinTrans- Trans-

criptioncription

Trans- Trans-

lationlation

Repli-Repli-cationcation

Synthesis phase: DNA replication Semiconservative replication: every double helix contains a parent strand and a newly synthetised one.

Parent

First generation

Second generation

Synthesis of the complementary daughter DNA strands

5’

5’

3’

3’

Daughter duplex

Daughter duplex

Direction of fork

Parental DNA duplex

5’

3’ 5’

3’

Leading strand

Lagging strand

Okazaki fragments connected by DNA ligase

DNA polymerases carry out DNA synthesis on a DNA template, exclusively in 5’ to 3’ direction.

DNA polymerases are unable to initiate de novo DNA synthesis, but can add nucleotides to the 3’end of preexisting RNA or DNA strands (RNA primerRNA primer, synthetised by the enzyme primase).

5’ 3’

Leading strand template

RNA primer, ~10 nucleotides long in eukaryotes

Leading strand: DNA synthesis is continuous

Leading strand

Lagging strand: DNA synthesis is discontinuous

5’ 3’

Lagging strand template

5’3’

replication fork

New RNA primerOkazaki fragment (~200 nucleotides)

3’5’ 3’

New Okazaki fragment building up

3’5’ 3’

New Okazaki fragment finished

3’5’ 3’

Old primer erased and replaced by DNA

3’5’ 3’

Nick sealing by DNA ligase joins new Okazaki fragment to the growing strand

DNA repair, mutations

Maintainig genetic stability requires accurate mechanism of replication as well as repair of lesions that occur continually in DNA. Most spontaneous changes are immediately corrected by the complex process of DNA DNA repairrepair. DNA repair, similarly to replication, relies on base-pairing and involves several different pathways. If this process fails, permanent change – mutation mutation – occurs in DNA. Mutations in vital positions of the DNA sequence destroy the organism, others might cause advantageous modifications in the gene products, contributing to the driving force of the evolution.

G1 PhaseG1 Phase:: the cell contains 2C DNA content, one set of DNA from each parent (number of chromosomes: 2n), thus the cell is diploid.

End of S Phase:End of S Phase: As a result of DNA replication, the cell contains two sets of 2C DNA (number of chromosomes: 4n, transitory tetraploid status).

G2 PhaseG2 Phase:: the cell grows and prepares for division

M Phase:M Phase: division:mitosis:mitosis: a single 4n parent cell gives rise to two identical daughter cells with 2n chromosomesmeiosis:meiosis: a single parent cell gives rise to four gamete cells each with n chromosomes

Types of cell division:Types of cell division:

1./ Without formation of chromosomes: 1./ Without formation of chromosomes: direct (mainly pathologic):direct (mainly pathologic):amitosis: nuclear material is distributedamitosis: nuclear material is distributed

at random to the resultant cellsat random to the resultant cells

2./ With formation of chromosomes: 2./ With formation of chromosomes: indirectindirectA./ mitosis (division of somatic cells)A./ mitosis (division of somatic cells)B./ meiosis (ovum and spermium)B./ meiosis (ovum and spermium)

Sister chromatids

Shorter arm

Longer arm

THE STRUCTURE OF DUPLICATED CHROMOSOMES THE STRUCTURE OF DUPLICATED CHROMOSOMES AS SEEN IN METAPHASEAS SEEN IN METAPHASE

Human karyotype: n=23, 2n=46Human karyotype: n=23, 2n=46

Attachment site:

kinetochorkinetochor at the centromer

A chromosome consisting two identical sister chromatidsA chromosome consisting two identical sister chromatids

Interphase: chromatin spreadout in indistinct mass. Nucleusand nucleolus distinct.

Prophase: Chromatin condense and visible as set of sister chromatidsNucleolus and nuclear envelope disappear. Spindle appears.

Metaphase: mitotic spindle complete. Chromatid sets moveto spindle equator.

Anaphase: kinetochors dividesister chromatids form individualchromosomes moving to opposite poles of the spindle.

Telophase: two new nuclei form.Division of cytoplasmbegins.

Cytokinesis: microfilamentsconstrict cell at equatorpinching it in two.

SSTTEEPPSS

OOFF

MMIITTOOSSIISS

Phases of mitotic divison:Phases of mitotic divison:

1. Prophase1. Prophase

2. Metaphase:2. Metaphase:

3. Anaphase:3. Anaphase:

4. Telophase4. Telophase

MEIOSISMEIOSIS

Only occurs in sexual cells in the gonads (ovaries and testes).Only occurs in sexual cells in the gonads (ovaries and testes).

Reason: during the formation of gametes (sperm and egg)Reason: during the formation of gametes (sperm and egg)the genomic DNA content and the corresponding the genomic DNA content and the corresponding chromosome number of the gametes must be reducedchromosome number of the gametes must be reducedby half. Gametes are haploid (n) with a DNA content of 1C.by half. Gametes are haploid (n) with a DNA content of 1C.During fertilization the joining of the two haploid gametesDuring fertilization the joining of the two haploid gameteswill re-establish the diploid number of chromosomes andwill re-establish the diploid number of chromosomes andthe 2C DNA content (one set from each parent).the 2C DNA content (one set from each parent).

Phases of meiosis:Phases of meiosis:Meiosis occurs in two phases: Meiosis I. (Reduction division)Meiosis occurs in two phases: Meiosis I. (Reduction division)

and Meiosis II. (Division)and Meiosis II. (Division)

Meiosis I.Meiosis I.Prophase:Prophase:Leptotene (thin thread) stage:Leptotene (thin thread) stage: the thread-like chromatin

has not condensed

Meiosis I.Meiosis I.Prophase:Prophase:Zygotene (yoked thread) stageZygotene (yoked thread) stage: the homologous chromosomes align side-by-side in a process of pairing called synapsis. Thisrelationship is called a tetrad or bivalent.

Meiosis I.Meiosis I.Prophase:Prophase:Pachytene (thick thread) stage:Pachytene (thick thread) stage: condensation of chromosomes

crossing over can happen

Meiosis I.Meiosis I.Prophase:Prophase:Diplotene (double threads) stageDiplotene (double threads) stage:: homologous chromosomes begin to separate remaining attached at areas called chiasmata

Meiosis I.Meiosis I.Prophase:Prophase:Diakinesis (moving apart):Diakinesis (moving apart): the centromeres move away fromeach other leaving the chromosomes attached only at their tipsAt this point the nuclear envelope breaks down.

Meiosis I.Meiosis I.Metaphase: Metaphase: the asters have moved to opposite sides of the cell and have formed the meiotic spindle that is composed of microtubules

Meiosis I.Meiosis I.Anaphase: Anaphase: the homologous chromosomes are pulled to the poles by active sliding of the microtubules. This results in the separation of the homologous chromosomes to separate cells.

Meiosis I.Meiosis I.Telophase: Telophase: two daughter cells are formed, each containing one partner of each of the homologous chromosome pairs. The nuclear envelope reforms as the chromosomes decondenseand nucleolus reappears.

Meiosis II.Meiosis II.Prophase: Prophase: following a short interkinesis in which no DNA synthesis occurs, the second meiotic division begins: the chromosomes condense and the nuclear envelope breaks down and the spindle reforms.

Meiosis II.Meiosis II.Metaphase: Metaphase: the condensed chromosomes align along the metaphase plate with the centromeres attached to the spindle microtubules

Meiosis II.Meiosis II.Anaphase: Anaphase: the chromosomes are pulled to the poles resulting the division of the centromere so that each the sister chromatidsgoes to the opposite poles.

Meiosis II.Meiosis II.Telophase: Telophase: each sister chromatid is konwn as a singlechromosome. Thus the resulting haploid cells each contain a haploid genome. The chromosomes have sparated. The spindle disappears, nuclear envelope reforms and the cell membrane beginsto pinch in.

Haploid daughter cells

SUMMARY OF THE STEPS SUMMARY OF THE STEPS OF MEIOTIC DIVISIONOF MEIOTIC DIVISION

Microtubule dynamics and motor proteinsMicrotubule dynamics and motor proteinsduring mitosis:during mitosis:Microtubule apparatus:Microtubule apparatus: - a microtubule machine for separating chromosomes constantly changing during mitosisParts of the mitotic apparatus:Parts of the mitotic apparatus:- central spindlecentral spindle: bilaterally symmetric bundle of microtubules divided in two halves by the plate of metaphase chromosomes- a pair of asters:asters: a tuft of microtubules at each pole of the spindle- astral microtubules:astral microtubules: form the aster, help to position the mitotic

apparatus and to determine the cleavage plane during cytokinesis

- kinetochore microtubuleskinetochore microtubules attach to the chromosomes- polar microtubulespolar microtubules interdigitate with polar microtubules of the

opposite pole

Theasurus :Theasurus :

Homologous chromosomes:Homologous chromosomes: members of a pair, one from the mother’s, one from the father’s sideHomozygote:Homozygote: both members of the pair contain the same information concerning a given featureHeterozygote:Heterozygote: the members of the pair contain different information about a given featureSister chromatids:Sister chromatids: the two identical parts of a chromosome after the S-phase of the cell cycle, as seen at metaphaseKinetochor:Kinetochor: plate-like structure lying within a small highly specialized region of the chromosome, the centromereCentrosome:Centrosome: the microtubule organizing center