CHAPTER 3, PART 1

Cell Division

Cell Division; Mitosis

• Mitosis produces two identical daughter cells that are exact replicas of the parental cell

• Most body cells are somatic cells (non-reproductive), usually with chromosomes present in pairs, the number of chromosomes is the diploid number (2n)

• Meiosis produces gametes that have half the number of chromosomes as the original cell: haploid (n)

• The gametes are not identical to one another

• Basis for sexual reproduction; genetic diversity is the adaptive advantage of sex! Aids evolution!

Cell Division (Reproductive Cells); Meiosis

• Diploid cells carry two sets of genetic information. • Where are they coming from?

• Haploid cells carry one set of genetic information.

Homologous Pair

Locus; location of specific gene

Homologous vs. Non-homologous Chromosomes

Homologous Chromosomes / Homologs

Homologous chromosomes (homologs) = members of a chromosome pair that are identical in the arrangement of genes they contain (but might have different alleles) – i.e. 2 copies of chromosome #1. Homologs pair during meiosis!

Non-homologous chromosomes = chromosomes that contain different genes and do not pair during meiosis

Non-homologous Chromosomes

Gene Order on Homologous Chromosomes

Homologous chromosomes contain the same genes in the same order

Gene A

Gene B

Gene C

Gene D

Gene E

Gene F

Are the DNA sequences of homologous completely identical?

No! can have different alleles!

Chromosome Structure Overview

• Centromere: attachment point for spindle microtubules• Telomeres: tips of a linear chromosome. Provide

chromosomal stability• Limits Cell Division; over time telomeres become shorter• Aging and Cancer• 2009 Nobel Prize awarded to E. Blackburn

• Origins of replication: where the DNA synthesis begins

Chromosomal Classification and the Position of The Centromere

What is a possible difference between two homologs?

A. Different genesB. Different lengths C. Different loci for

allelesD. Different

centromere positions

E. Different allelesF. All of the above Diff

erent g

enes

Differe

nt length

s

Differe

nt loci

for alle

les

Differe

nt centro

mere pos..

.

Differe

nt alle

les

All of t

he above

17% 17% 17%17%17%17%

3.1 Mitosis Divides Somatic Cells

• Mitosis is the process of cell division that produces two genetically identical daughter cells from one original parental cell

• It is preciselyprecisely controlled to prevent either an excess or insufficient number of cells

• Rate of division is important

• Too slow: failure to develop, morphological abnormalities

• Too fast: growth of structures beyond boundaries (cancer!)

• Both: Death!

Stages of the Cell Cycle

• Cell division is regulated by control of the cell cycle, a cycle of DNA replication and division

• Cell cycles of all eukaryotes are similar

• The two principal phases of the cell cycle are M phase, the short time during which the cells divide and a longer interphase, the time between M phases

Inte

rph

ase

Ex. Neurons, eye cells, certain bone cells

G zero

Interphase

• During the Gap 1 (G1) phase of interphase, all proteins needed for normal cell function are transcribed and translated; the duration of G1 varies

• DNA is replicated during S phase or synthesis phase, which follows G1

• Two sister chromatids are produced!

• A small number of cells enter G0 after G1; cells in G0 never progress through the cell cycle

• The completion of S phase leads into G2 or Gap 2 phase, during which the cells prepare for division

www.nature.com

DNA ReplicationThe chromosomes are replicated prior to cell division

1 chromosome

The two strands are completely identical

Homologous Chromosomes

Circle 1 chromosom

e after replication

What do you call these two identical strands?

Why?

Sister Chromatids

Sister Chromatids: The 2 subunits of a replicated chromosome.

Non-sister Chromatids: chromatids from different chromosomes

- They should be identical.

Find a pair of non-sister chromatids

Sister Chromatids

Non-sister chromatids

Sister Chromatids are IDENTICAL!

Homologous before replication

Homologous after replication

A

Bc C

b

a

What alleles will be on

each chromatid?

A A

B B

cc

a a

b b

CC

If 1 sister has “A”, the other sister will too, etc

Chromosomes During Mitosis

• Cells at the beginning and the end of mitosis are diploid (2n)

• Progressive condensation of chromosomes begins in prophase and reaches a maximum in metaphase

• Centromeres, specialized sequences where sister chromatids are joined together, become visible in prophase; centromeres bind protein complexes called kinetochores

DNA in blueMicrotubules in greenKinetochores in pink

Substages of M Phase

• M phase is divided into

• Prophase

• Prometaphase

• Metaphase

• Anaphase

• Telophase

• M phase accomplishes karyokinesis, partitioning of DNA into daughter cell nuclei and cytokinesis, the partitioning of the cytoplasm

Study Figure 3.2!

Chromosome Distribution

• In animal cells, two centrosomes appear, which migrate to form the opposite poles of the dividing cell

• Centrosomes are the source of microtubules; microtubules have a minus (-) end at the centrosome and a plus (+) end that grows away from the centrosome

• The spindle fibers emanate from the centrosomes in a pattern called the aster

Types of Microtubules in Cells

1. Kinetochore microtubules embed in the kinetochore at the centromere of each chromatid, and are responsible for chromosome movement

2. Polar microtubules extend toward the opposite pole of the centrosome and contribute to cell elongation and cell stability

3. Astral microtubules grow toward the membrane of the cell, and contribute to cell stability

Metaphase Chromosomes

• By the end of prometaphase, kinetochore microtubules are bound to each kinetochore

• Metaphase chromosomes are 10,000-fold condensed compared to the onset of prophase; these chromosomes are pulled toward each centrosome by the kinetochore microtubules

• The opposing forces align the chromosomes along the metaphase plate

http://staff.jccc.net/pdecell/celldivision/mitosis1.html

Sister Chromatid Cohesion

• Sister chromatid cohesion • Balances tension created

by pull of kinetochore microtubules

• Cohesin holds sister chromatids together, preventing their premature separation• 4-subunit protein • coats sister chromatids

along their entire length• greatest concentration at

the centromeres

Anaphase

• Sister chromatids separate at anaphase and begin to move toward opposite poles in the cell

• In anaphase A the sister chromatids separate due to the enzyme separase cleaving Scc1, the central component of cohesin

• The separation of sister chromatids is called chromosome disjunction

Anaphase, continued

• During anaphase, polar microtubules extend in length, causing an extended shape

• The altered shape facilitates cytokinesis at the end of telophase, leading to formation of two daughter cells

Completion of Cell Division; Telophase

• In telophase, nuclear membranes reassemble around the chromosomes at each pole

• Decondensation returns chromosomes to their diffuse interphase state

• Two identical nuclei occupy the elongated cell

What’s Next?

Cytokinesis

• In animal cells, a contractile ring of actin creates a cleavage furrow around the circumference of the cell; this pinches the cell in two

• In plants, a new cell wall is constructed along the cellular midline

• In both, cytokinesis divided the cytoplasm and organelles between the daughter cells

Mitosis Produces Identical Daughter Cells

• Mitosis separates replicated copies of sister chromatids into identical nuclei, forming two genetically identical daughter cells

• The diploid number of chromosomes (2n) is maintained throughout the cell cycle

# ofchromatids

Cell Cycle Checkpoints

• Common, genetically controlled signals drive the cell cycle

• Cell cycle checkpoints are monitored by protein interactions for readiness to progress to the next stage

• A common mechanism is carried out by protein complexes joining a protein kinase with a cyclin protein

What happens if we lose control of the cell cycle?

What happens if we lose control of the cell cycle?

Cyclins and Cdks

• Protein kinase components of the complexes are activated by association with cyclins and so are called cyclin-dependent kinases (Cdks)

• Multiple cyclin and Cdks form a variety of complexes

• For example, cyclin B-Cdk1 is required to initiate M phase; the complex also activates an enzyme that degrades cyclin B

WHAT IF WE LOSE CONTROL OF THE CELL CYCLE?

Cyclins control the cell cycle.

HOW CAN WE ALTER THE SPEED OF THE CELL CYCLE?

The RB1 Gene Is a Tumor Suppressor Gene

• The unphosphorylated Retinoblastoma protein (pRB) acts like a brake on the cell cycle, preventing progression to S phase

• It is one of many proteins known as tumor suppressors, with roles in blocking the cell cycle

• The gene RB1, which produces pRB, is a tumor suppressor gene

Proto-oncogenes are the green light for the cell cycle!Proto-oncogenes are the green light for the cell cycle!

The Cyclin D1 Gene Is a Proto-Oncogene

• The gene cyclin D1 leads to formation of the cyclin D1-Cdk4 complex that stimulates the cell cycle to enter S phase

• Cyclin D1 is a proto-oncogene, defined as a gene that when expressed stimulates cell cycle progression

Cell Cycle Mutations and Cancer

• Normal cells proliferate only when needed, in response to signals from growth factors

• They are also responsive to neighboring cells; growth is moderated to serve the best interests of the whole organism

• Cancer is characterized by out-of-control proliferation of cells that can invade and displace normal cells

Oncogenes are the gas pedal STUCK ON! Oncogenes are the gas pedal STUCK ON!

Mutations Related to Cancer Development

• Cancer-causing mutations alter cyclin D1-Cdk4 and pRB interactions

• Some mutations increase the number of copies of cyclin D1, now an oncogene!

• Higher-than-normal levels of cyclin D1 promote uncontrolled entry into S phase, due to constant phosphorylation of pRB

http://www.broadinstitute.org

Mutations Related to Cancer Development

• Another mutation affects RB1; it produces a pRB that binds weakly or not at all to E2F• Can lead to uncontrolled

entry into S phase

• This is loss of a tumor-suppressor gene!

• Several types of cancers are associated with RB1 mutations, including retinoblastoma, and bladder, lung, bone, and breast cancers

AND NOW ON TO MEIOSIS…

3.2 Meiosis Produces Gametes for Sexual Reproduction

• Reproduction can be divided into two broad categories:

• In asexual reproduction, organisms reproduce without mating and produce genetically identical offspring

• In sexual reproduction, gametes (reproductive cells) are produced; these unite during fertilization

Multicellular Eukaryotes Reproduce Mainly Sexually

• Males and females carry distinct reproductive tissues and structures

• Mating requires the production of haploid gametes from both male and female

• The union of haploid gametes produces diploid progeny

Meiosis versus Mitosis

• Meiosis is distinguished from mitosis as it results in the production of four haploid gametes

• Meiotic interphase is followed by two division stages called meiosis I and meiosis II.

• No DNA replication between these stages!

Meiosis I vs. II

In meiosis I homologous chromosomes separate; reducing the diploid number of chromosomes to the haploid number

In meiosis I homologous chromosomes separate; reducing the diploid number of chromosomes to the haploid number

In meiosis II, sister chromatids separate to produce four haploid gametes

In meiosis II, sister chromatids separate to produce four haploid gametes

Meiosis I

• Three hallmark events occur in meiosis I

1. Homologous chromosome pairing

2. Crossing over between homologous chromosomes

3. Segregation (separation) of homologous chromosomes, which reduces chromosomes to the haploid number

Stages of Meiosis I

• Meiosis I is divided into prophase I, metaphase I, anaphase I, and telophase I

• Pairing and recombination of homologs takes place in prophase I

• Prophase I is subdivided into five stages: leptotene, zygotene, pachytene, diplotene, and diakinesis

On to Pachytene….

Prophase I has five stages….

Synaptonemal complex!

Synaptonemal complex: -occurs between nonsister chromatids of homologous chromosome-contains the recombination nodule, essential for crossing over of genetic material

Metaphase I

• In metaphase I chiasmata between homologs are dissolved; this completes crossing over

• Homologs align on opposite sides of the metaphase plate

http://www.phschool.com

Anaphase I

• Anaphase I begins when homologs separate from one another and are pulled to opposite poles of the cell

• Sister chromatids are firmly attached by cohesin

http://www.phschool.com

Telophase I and Cytokinesis

• In telophase I the nuclear membranes reform around the separated haploid sets of chromosomes

• Cytokinesis follows telophase I and divides the cytoplasm to create two haploid cells

• Meiosis I is called the reductional division because the ploidy of the daughter cells is halved compared to the original diploid parent cell

Reduction Division!

Meiosis II

• Meiosis II divides each haploid daughter cell into two haploid cells, by separating sister chromatids from one another

• The process is similar to mitosis in a haploid cell• Four genetically distinct haploid cells are produced, each carrying one

chromosome of a homologous pair

The Mechanistic Basis of Mendelian Ratios

• Separation of homologs and sister chromatid in meiosis constitutes the mechanical basis of Mendel’s laws

• For example, in an organism that is genotype Aa, the homologs bearing A and a separate from one another during anaphase I

• At the end of meiosis, two gametes have the A allele and two have a; this generates the 1:1 ratio predicted by the law of segregation

IndependentAssortmentIndependentAssortment

Questions?