Spring 2009: Section 3 – lecture 2 Reading – Chapter 3 Chapter 10, pages 251 - 267

Cell Cycle and Cell Division Four phases or stages G1 – growth stage 1 S - synthesis stage G2 – growth stage 2 M – cell division (mitosis or meiosis)

G1 phase production of components for DNA replication S phase DNA replication starts

G2 phase DNA replication continues production of the components for cell division M phase cell division, either mitosis or meiosis

Regulation of the cell cycle To insure that DNA synthesis and component production has occurred before mitosis or meiosis starts, it is necessary to have some form of cell cycle regulation. Some system is needed to signal the start of mitosis and the end of mitosis.

One such system involves the synthesis and degradation of specific proteins in the cell. Primary proteins involved are: - cyclin - cdc2 (cell division cycle) and other cdc proteins - MPF – M phase promoting factor

MPF – M phase promoting factor - combination of cyclin and cdc2 - can be present in two forms, inactive and active - activation occurs through phosphorylation of cyclin subunit and dephosphorylation of the cdc2 subunit

The presence of MPF triggers mitosis, the breakdown of the nuclear membrane, and cyclin degradation. The absence of cyclin allows mitosis to end. As mitosis ends cyclin and MPF are low.

Cell cycle regulation by MPF early interphase - low cyclin concentration - low MPF concentration intermediate interphase - synthesis of cyclin - combination of cyclin and cdc2 to produce inactive MPF late interphase - continued increase in MPF - activation of MPF

Cell cycle regulation by MPF early mitosis - presence of active MPF starts breakdown of the nuclear membrane and signals start of mitosis - degradation of cyclin component starts mid- mitosis - cyclin degradation causes decrease in both MPF and cyclin late mitosis - reduction in cyclin and MPF signals end of mitosis and allows for reformation of the nuclear membrane

The level of phosphorylation of cdc2 may influence both the start of the S phase as well as the start of the M phase. - phosphorylated cdc2 needed to start S phase - dephosphorylated cdc2 needed to start M phase

Interference with production of cyclin or the phosphorylation or dephosphorylation of components of MPF can lead to disruption of the cell cycle. This has been demonstrated using mutants for the various components.

Condensing of the chromosomes at the start of the M phase is facilitated by two proteins, condensin and cohesin, that are SMC (structural maintenance of chromosome) proteins Condensin – aids in the organization of the highly condensed chromosomes Cohesin – holds the sister chromatids until the first stage of the M division (prophase)

Mitosis – Cell division that results in daughter cells having the same amount of DNA as the original parent cell. Stages of mitosis - prophase - metaphase - anaphase - telophase

Interphase Chromatin not condensed Nuclear membrane present Nucleolus present

Prophase Sister chromatids start to condense Spindle fibers start to form Nuclear membrane and nucleolus start to disappear

Metaphase Sister chromatids condensed Sister chromatids align on the metaphase plate No nucleolus, no nuclear membrane

Anaphase Sister chromatids separate to form daughter chromosomes Daughter chromatids start to migrate to the poles, centromere first

Sister Chromatids Daughter Chromosomes Metaphase Anaphase

Telophase Daughter chromosomes reach the the spindle poles Chromatin starts to relax Nuclear membrane starts to reform Nucleolus becomes visible

Meiosis – Cell division where the chromosome number is reduced by half. This is accomplished by having one cycle of chromosome replication followed by two divisions By reducing the number of chromosomes the cells go from a somatic number of 2N to a gametic number of N

The two divisions are designated the reduction division and the equational division. – separation of homologous chromosomes. This is the division when the chromosome number is reduced.

Equational division - separation of sister chromatids. This results in four cells having half the number or chromosomes as the original cell.

Reductional Division In this division the chromosome number is reduced and recombination between homologous chromosomes can occur. There are four stages: - prophase I - metaphase I - anaphase I - telophase I

To describe everything that occurs in prophase I it is divided into five sub-stages: - leptotene - zygotene - pachytene - diplotene - diakinesis

Leptotene chromosomes become visible telomeres are in contact with the nuclear membrane nucleolus present

Zygotene chromosomes continue to condense homologous chromosomes pair pairing is known as synapsis Nucleolus and nuclear membrane are still present

The homologous chromosomes are held together by the synaptonemal complex. The synaptonemal complex is a tripartite ribbon made of two lateral protein bands surrounding a medial protein complex. The synaptonemal complex makes it possible for recombination to occur.

Pachytene paired chromosomes continue to condense and shorten exchange between non-sister chromatids can occur exchange appears to be protein mediated nucleolus and nuclear membrane still present

Diplotene - synaptonemal complex starts to break down homologous chromosome pairs start to separate areas of exchange stay together longer, called chiasma Nucleolus and nuclear membrane start to breakdown

Diakinesis - chromosomes continue to condense and chiasmata terminalize if chiasmata in both arms get a ring bivalent, if one arm a rod bivalent nucleolus and nuclear membrane start to disappear

Formation of ring bivalent with terminalization of chiasmata Formation of rod bivalent with terminalization of chiasmata

Metaphase I bivalents align on metaphase plate presence of multiple chromosomes pairing or chromosomes not pairing are indicators of chromosome additions, deletions or modifications

Rod bivalents Ring bivalents Univalents