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Cell Cycle, Mitosis & Meiosis

Chromosomes

All eukaryotic cells store genetic information in chromosomes.• Most eukaryotes have between 10 and

50 chromosomes in their body cells.• Human cells have 46 chromosomes.• 23 nearly-identical pairs

Chromosomes A diploid cell has two sets of each of its chromosomes A human has 46 chromosomes (2n = 46) In a cell in which DNA synthesis has occurred all the

chromosomes are duplicated and thus each consists of two identical sister chromatids

Maternal set ofchromosomes (n = 3)

Paternal set ofchromosomes (n = 3)

2n = 6

Two sister chromatidsof one replicatedchromosome

Two nonsisterchromatids ina homologous pair

Pair of homologouschromosomes(one from each set)

Centromere

Chromosome Duplication

0.5 µm

Chromosomeduplication(including DNA synthesis)

Centromere

Separation of sister

chromatids

Sisterchromatids

Centrometers Sister chromatids

A eukaryotic cell has multiplechromosomes, one of which is

represented here. Before duplication, each chromosome

has a single DNA molecule.

Once duplicated, a chromosomeconsists of two sister chromatids

connected at the centromere. Eachchromatid contains a copy of the

DNA molecule.

Mechanical processes separate the sister chromatids into two chromosomes and distribute

them to two daughter cells.

In preparation for cell division, DNA is replicated and the chromosomes condense

Each duplicated chromosome has two sister chromatids, which separate during cell division

Because of duplication, each condensed chromosome consists of 2 identical chromatids joined by a centromere.

Each duplicated chromosome contains 2 identical DNA molecules (unless a mutation occurred), one in each chromatid:

Chromosome Duplication

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Two unduplicatedchromosomes

Centromere

Sisterchromatids

Sisterchromatids

Duplication

Non-sisterchromatids

Two duplicated chromosomes

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Chromosomes, ploidy and n

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2 Types of Cell Division

Mitosis – ordinary somatic cell division• 2 daughter cells with identical

chromosomes and genes to parents• Diploid cells – 2n chromosome

complement Meiosis – germline cell division

• Results in formation of gametes – cells with only 23 chromosomes

• Haploid cells – n chromosome complement

Phases of the Cell Cycle Interphase• G1 - primary growth • S - genome replicated• G2 - secondary growth

M - mitosis C - cytokinesis

Interphase

G1 - Cells undergo majority of growth

S - Each chromosome replicates (Synthesizes) to produce sister chromatids• Attached at centromere• Contains attachment site (kinetochore)

G2 - Chromosomes condense - Assemble machinery for division such as centrioles

Mitosis Some haploid & diploid cells divide by

mitosis. Each new cell receives one copy of every

chromosome that was present in the original cell.

Produces 2 new cells that are both genetically identical to the original cell.

DNA duplication

during interphase Mitosis

Diploid Cell

Embryonic cell cycles The duration of the phases

varies considerably in different kinds of cells.

Early embryos may have cell cycles of 30 minutes, but there is no growth (G1 or G2) phase.

In contrast, some cells in adult animals cease division altogether (e.g., nerve cells).

Others may divide only occasionally, to replace cells that have been lost.

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The Cell Cycle

G1

• No DNA synthesis• Lasts hours, days or years• Occurs after mitosis and before S phase

The availability of growth factors controls the animal cell cycle at a point in late G1 called the restriction point. If growth factors are not available during G1, the cells enter a quiescent stage of the cycle called G0.

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The Cell CycleS phase

• Stage of DNA synthesis• The major variants of histones are predominantly

synthesized during S phase• Each chromosome replicates bipartite

chromosome made up of sister chromatids• End of each chromatid marked by telomeres –

specialized DNA sequences that ensure integrity of chromosomes during division

• Sister chromatids held together at centromere – region of DNA associated with kinetochore

• DNA replication happens at thousands of origins of DNA replication

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The Cell Cycle

G2 phase• The cell is preparing for mitosis• Cell’s DNA doubled in S phase• Brief stage

G0 phase• Resting stage/quiescent stage • Neurons, RBCs arrested in G1 = G0 phase

– permanent G1 phase • Liver cells enter G0 but on damage G1 and

cell cycle continues

Figure 17-31 Molecular Biology of the Cell (© Garland Science 2008)

Centriole Replication

At a certain point in G1, the two centrioles of the pair separate.

During S phase, a daughter centriole begins to grow near the base of each mother centriole and at a right angle to it.

The elongation of the daughter centriole is usually completed by G2

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Mitosis

Mitosis: shortest of 4 stages Important component: chromosomal

segregation – process of distributing copy of each chromosome to each daughter cell

Errors genetic imbalances, tumors 5 stages:

1. Prophase2. Prometaphase3. Metaphase4. Anaphase5. Telophase

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Mitosis is subdivided into prophase, prometaphase, metaphase, anaphase, and

telophase

Prophase: Condensed chromosome start to become visible, Centrosomes start moving apart, Nucleolus starts disappearing

Prometaphase: Nuclear membrane breaks down

Metaphase: Chromosomes maximally condensed and align at the metaphase plate

Anaphase: The two sister chromatids separate and move toward opposite poles

Telophase: nucleus reassembly occurs, cytokinesis occurs

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Stages of mitosis in an animal cell

Fluorescence micrographs of chromatin, keratin, and microtubules during mitosis

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Prophase Condensation of chromosomes Disintegration and disappearance of nucleolus Formation of mitotic spindle – microtubule

network

Prometaphase Nuclear membrane breaks up Congression occurs – chromosomes move

to point midway between spindle poles Condensation of chromosomes continue

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Metaphase Maximum condensation of chromosomes

reached Arranged at equatorial plane of cell Balanced forces of microtubules from

opposite poles at kinetochores

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The mitotic spindle is responsible for chromosome movements during mitosis

Spindle assembly and chromosome attachment• Minus ends anchored in

centrosome• Kinetochore: a platelike,

three layer structure made of proteins attached to CEN sequences located in the centromeres’ DNA

• Two kinetochores are located on opposite sides of a chromosome and anchor kinetochore microtubules

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Anaphase Begins when sister

chromatids separate Sister chromatids

separate into daughter chromosomes

Daughter chromosomes move to opposite poles

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Telophase and Cytokinesis Telophase

• Chromosomes decondense• Nuclear membrane reforms

Cytokinesis divides the cytoplasm • Cleavage begins as a slight

indentation in cell surface deepens into a cleavage furrow.

• Actin contractile ring and myosin motors drive the process

• Cytoplasm cleaves separating daughter cells

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Meiosis One round of DNA synthesis

2 rounds of chromosomal segregation• Meiosis I – reduction division

– chromosome no. goes from diploid haploid

Meiotic crossing over or recombination also occurs here: homologous segments of DNA exchanged between nonsister chromatids of pair of homologous chromosomes

Recombination important also for chromosome segregation

• Meiosis II – like mitosis without a preceding DNA replication stage

Sister chromatids separate

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Meiosis Meiosis can convert one diploid cell into four

haploid cells• Meiosis I: the first meiotic division• Homologous pairs join together to form a bivalent

Meiosis I produces two haploid cells that have chromosomes composed of sister chromatids• Unlike mitosis, in meiosis I, sister chromatids stay

together. • Thus, the cells at the end of meiosis I are

considered haploid because it contains only one of the two chromosomes of each bivalent

• Genetic recombination

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Meiosis I

Prophase I: Homologous chromosomes become paired and exchange DNA• Divided into 5 stages• Formation of synaptonemal complex and crossing-over occurs

Metaphase I: Bivalents align at the spindle equator• The kinetochores of sister chromatids lie side by side and face

the same pole of the cell• Random orientation of maternal or paternal chromosomes• Chromosomes held together by chiasmata

Anaphase I: Homologous chromosomes move to opposite spindle poles

Telophase I and cytokinesis: Two haploid cells are produced

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Prophase I Leptotene

• chromatin begins to condense, 2 sister chromatids so close, cannot be distinguished

Zygotene• Homologs pair along entire length – synapsis• Chromosomes held together by synaptonemal complex

Pachytene• Synapsis complete, chromosome more tightly coiled• Chromosome appear bivalent – tetrad formation• Recombination takes place

Diplotene• Synaptonemal complex disappears• Bivalents begin to separate but held together at centromeres

and ~ 50 points of crossing over – chiasmata Diakinesis – stage of max condensation

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Bivalent Formation and Crossing-over

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Anaphase I Disjunction occurs – members of each bivalent move

apart• HOMOLOGS (and usually alleles) SEPARATE!!!

Maternal and paternal chromosomes sort independently 223 combinations• Add to this the variation due to crossing over e.g. chr 1 typically

contains 3-5 segments Error-prone step: particularly nondisjunction

Metaphase I Nuclear membrane disappears Spindle forms Bivalents align at equator

Chromosome segregation in meiosis I

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Telophase I & Cytokinesis

Telophase I – 2 chromosome sets group at opposite poles

Cytokinesis – cell divides into daughter cells enter meiotic interphase (no DNA synthesis)• Spermatogenesis: equal• Oogenesis: secondary oocyte receives

most cytoplasm, other cell 1st polar body

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Meiosis II Meiosis II resembles a mitotic division Prophase II is very brief Metaphase II

• Kinetochores of sister chromatids now face in opposite directions

Anaphase II• Sister chromatids separate

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Genetic Consequences of Meiosis At the end of meiosis II there are four daughter

cells, each containing a haploid set of chromosomes• Reduction of chromosome number

Segregation of alleles Random assortment of the homologues (law of

independent assortment) • Meiosis generates genetic diversity • Over 8 million different combinations of

chromosomes Additional shuffling by crossing over Nondisjunction refers to the failure of the two

members of a homologous chromosome pair to separate during anaphase• Leads to aneuploidy diseases (trisomy 21-Down

syndrome)

Solve This Question A couple in their late 30's has a baby girl with a

trisomy 21 karyotype. Genetic analysis of a polymorphic VNTR locus on chromosome 21 reveals that the baby has allelic variants A, C, D; the mother has alleles A, D; the father has alleles B, C. When did meiotic nondisjunction most likely occur and in which parent?

Answer: Nondisjunction occurred during meiosis I in the mother.

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Comparison of meiosis and mitosis

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Human Gametogenesis

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Spermatogenesis Sperm formed in seminiferous tubules after sexual maturity Tubules lined with spermatogonia in different stages of

differentiation Last cell type is primary spermatocyte meiosis I 2 haploid

secondary spermatocytes meiosis II 4 spermatids sperm• Process takes 64 days• 200 million sperm produced per ejaculate and 1012 in a lifetime

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Oogenesis Occurs only during prenatal development Oogonia in ovarian cortex originate from

primordial germ cells by about 30 mitoses By 3rd month, oogonia primary oocytes which

enter prophase INo primary oocytes develop after month 5 of

fetal life At birth, ~ 2.5 million primary oogonia, only ~

400 eventually mature At sexual maturity, individual follicles mature,

oocyte completes meiosis I one secondary oocyte (ovum)

Meiosis II begins but is arrested in metaphase until fertilization

Oogenesis - Continued If fertilization takes place, this secondary oocyte will complete 2nd

meiotic division. Most of the cytoplasm is retained by the fertilized secondary oocyte

and the 2nd polar body receives very little cytoplasm. The 2nd polar body is extruded and maturation of oocyte is completed

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