Mitosis, Meiosis, and Cell Cycle

Mitosis and Meiosis

• Genetic material is a substance contained in every living thing, except for certain viruses where nucleic acid DNA is used
• An organism's DNA, along with its genes, is arranged into chromosomes, structures that help transmit genetic data.
• Mitosis and Meiosis, are two key processes involved in the genetic continuity of nucleated cells.

Cell Division

• Mitosis is the division of somatic cells
• Meiosis is the production of germ cells

Mitosis

• Results in the formation of two cells having the same number of chromosomes as the parent cell.

Meiosis

• Reduces the genetic content and the number of chromosomes by precisely half.
• The reduction is required for sexual reproduction to occur withouth doubling the amount of genetic material in each new generation.
• Mitosis is the portion of the cell cycle where the hereditary components are equally partitioned into daughter cells.
• Meiosis is a type of cell division leading to the production of sex cells (gametes or spores).

Chromosomes

• Visible during mitosis and meiosis
• When cells are not dividing, the genetic material of chromosomes uncoils into a loose network called chromatin within the nucleus.
• During mitosis and meiosis, chromatin fibers coil and condenses into chromosomes.

Nucleolus

• An amorphous component present in the nucleus where ribosomal RNA (rRNA) is synthesized and inital stages of ribosomal assembly occurs.
• Portions of DNA that encode rRNA are referred to as the nucleolus organizer region, or the NOR.

Centrioles

• Animal and some plant cells contains a pair of complex structures called centrioles.
• Centrioles are located in a specialized cytoplasmic region called the centrosome
• The centrosome is associated with the organization of spindle fibers that function in mitosis and meiosis.
• Spindle fibers play a key role in the movement of chromosomes as they separate during cell division

Chromosomes in Diploid Organisms

• Chromosomes are most easily visualized during mitosis due to their distinctive lengths and shapes
• Each chromosome contains a constricted region called the centromere.
• The shorter arm is above the centromere (p arm, for "petite").
• The longer arm is below the centromere (q arm).
• All somatic cells from members of the same species contain an identical number of chromosomes
• In most cases, this is the diploid number (2n).
• When lengths and centromere placements of chromosomes are examined, with the exception of sex chromosomes, they exist in pairs.
• With regard to these two properties, members of each pair are homologous chromosomes

Human Chromosomes

• Human mitotic chromosomes display are called a karyotype
• Humans have a 2n number of 46 exhibit a diversity of sizes and centromere placements.
• The 46 chromosomesconsist of two parallel sister chromatids connected by a centromere
• During cell division, the sister chromatids, replicates of each other, would have separated into the two new cells as division continued.

Haploid Cells

• The haploid number (n) of chromosomes is equal to one-half the diploid number
• The genetic information collectively contained in a haploid set of chromosomes makes up the genome of the species
• Copies of all genes, as well as a sizable amount of noncoding DNA.
• Homologous chromosomes have matching gene sites along their lengths
• Each site is called a locus (pl. loci).
• One member of each pair in sexually reproducing organisms from the maternal parent (through the ovum) and the other member is derived from the paternal parent (through the sperm).
• Each diploid organism contains two of each gene as a consequence of biparental inheritance, inheritance from two parents.
• During gamete formation, meiosis converts the diploid number of chromosomes to the haploid number.
• Following fusion of two gametes at fertilization, the diploid number is reestablished (zygote with two complete haploid sets of chromosomes).

Cell Division Process

• All living cells come from other living cells
• During mitosis, parent cell divides and forms two daughter cells with identical genetic information

Cell Cycle

• Chromosome complement of daughter cells is equal to that of the parent cell

Mitotic Cell Division Importance

• Mitotic cell division is required during development to make a new individual (successive divisions of fertilized egg; Zygote -> 10^13 cells are produced that make up the human body)
• Important for normal growth , renewal, regeneration, and repair in the adult body.
• Needed to replace cells that are lost due to wear and tear and programmed cell death to maintain the individual.

Mitosis Frequency

• Varies with the cell type
• Some cells divide frequently throughout life, such as rapidly renewing cells, including epithelium of the skin and intestinal epithelial cells (once a day).
• Some other cells divide very rarely (Once a year), such as liver cells and Pancreas (after an injury liver cells rapidly divide to repair a wound (until normal volume of the liver is restored))
• Mature humans have some cells that never divide long lived), these include nerve cells and hearth muscle cells.

Cell Cycle Stages

• Cell cycle consists of two major stages: mitosis and interphase
• Longest phase is interphase
• The cell requires much more time to grow and double their mass over the time it takes to duplicate their chromosomes and divide (mitosis lasts only one hour)

Phases of the Cell Cycle

• M phase (Mitosis) can be seen in a microscope (Morphological phase).
• Interphase consists of G1 phase (Gap1) Cell Growth, S phase (DNA synthesis), and G2 phase (Gap2) Preparation for mitosis.
• The cell cycle is M+ G1+ S+ G2.
• In rapidly dividing cell types, the cell cycle lasts 24 hours and the M phase lasts one hour

Mitosis Aim

• Somatic cells are diploid, so mitosis must produce two genetically identical and diploid daughter cells.

Mitosis Division-Cycle Requirements

• The cell must replicate (duplicate) its DNA.
• All cells must grow and duplicate all of their cytoplasmic contents
• They must segregate duplicated chromosomes to daughter cells.

G1 Phase (Gap1)

• Before the replication (between the mitosis and DNA replication).
• DNA amount is diploid: 2n
• RNA and protein synthesis occur.
• Cell Growth occurs
• Varies greatly depending on external conditions and extracellular signals from other cells
• If extracellular conditions are unfavorable, cells do not progress through G1 ,may enter a resting state known as Go (G zero)

S Phase

• G1 is followed by S phase
• Synthesis of DNA takes place
• At the end of S phase, DNA amount is doubled (4n).

G2 phase (Gap2)

• RNA and protein synthesis occurs
• Cell growth continues
• Proteins are synthesized in preperation for mitosis (i.e Tubulin)
• Cell contains 4n DNA (post duplication Phase)

Mitosis Events

• RNA and protein synthesis does not occur during Mitosis
• Cell structure undergoes dramatic alterations from the following events:
  • Chromosomes condense
  • Nuclear envelope breaks down
  • The cytoskeleton reorganizes to form mitotic spindle
  • Duplicated chromosomes (sister chromatids) separate and move to opposite poles
  • Two daughter nuclei form
  • Cytoplasm divides (Cytokinesis)

Mitosis Stages

• Mitosis consists of 6 stages: Prophase, Prometaphase, Metaphase, Anaphase, Telophase and Cytokinesis

Division-Cycle Requirements

• The cell must replicate (duplicate) its DNA to produce two genetically identical daughter cells
• All cells must grow and duplicate all of their cytoplasmic contents
• The cell must segregate duplicated chromosomes to daughter cells.

Prophase Events

• Beginning of prophase is marked by the appearance of condensed chromosomes (Long, thin thread like structures)
• A chromosome consists of two sister chromatids (produced in S phase), Chromatids attach together firmly
• Nucleolus disappears
• The 3-Breakdown of the nuclear envelope signals the end of Prophase
• Development of mitotic spindle initiates
• Centrosomes (duplicated during S phase) separate, move to opposite sites of the nucleus, and undergo maturation
• The Centrosomes serve as opposite poles of the mitotic spindle.

Prometaphase Events

• A transition period connecting prophase and metaphase
• Chromosomes become further condensed
• Chromosomes are thicker and shorter.
• The microtubules of the mitotic spindle attach to the kinetochores of chromosomes
• Spindle attachment sites, or kinetochores, of sister chromatids attach to microtubules emanating from spindle poles.
• Chromosomes move back and forth until they align on the metaphase plate

Metaphase Events

• Chromosomes align on the metaphase plate in the center of the spindle
• Cells remain only briefly at metaphase
• Two sister chromatids are held together only at the centromere

Anaphase Events

• Transition from metaphase to anaphase occurs
• Trigerred by Kinetochore division (as a result of breakdown of the links between sister chromatids (degradation of cohesins that link the chromatids)
• Then, sister chromatids separate and move to opposite poles of the spindle

Telophase Events

• Chromosomes decondense
• Division of nucleus ends completes with telophase
• Nuclei reform (nuclear envelope reform)
• Cytokinesis begins during anaphase
• Cytokinesis is complete by the end of telophase
• Spindle fibres disintegrate, Centrioles replicate, and the Nucleur membrane forms
• The cell divides

Cytokinesis Events

• The completion of mitosis gives rise to two daughter cells so the cytoplasm divides (Cytokinesis) begins during anaphase
• Mediated by a contactile ring of actin and myosin II filaments that forms beneath the plasma membrane at the equatorial plate of the spindle.
• Cleavage proceeds as contraction of actin-myosin filaments, which pulls the membrane inward and divides the cell in half

Mitosis Key Events

• Chromosome condensation
• Formation of mitotic spindle
• Sister chromatid resolution

Chromosomal Changes

• Condensation of interphase chromatin forms the compact chromosomes to create a is a key event of mitosis
• Required to enable the chromosomes to move along the mitotic spindle without broken or tangled with one another
• Chromatin condenses a thousandfold during the formation of metaphase chromosomes
• Chromatin condensation is induced by protein complexes called Condensins (a member of SMC; Structural Maintenance of Chromatin protein family)

DNA Molecules

• At the end of S phase, the long DNA molecules of the sister chromatids are tangled so that an attempt to pull the sister chromatids apart in this state would lead to breaks in the chromosomes.
• The cell expends energy in early mitosis to condense the sister chromatids into short, rod-like structures (chromosome condensation)

Condensin Function

• Condensin is a protein complex (SMC protein family)
• Condensins bind to DNA in M phase and induce chromatin condensation to form metaphase chromosomes
• Condensins can hydrolize ATP and coil DNA molecules in a test tube

Sister-Chromatid Cohesion

• Sister-chromatid cohesion depends on a large protein complex called cohesin
• Cohesin and condensin have a similar structure (SMC family members)
• Cohesin holds sister chromatids together
• Cohesins bind to DNA in S phase and maintain the linkage between the sister chromatids following replication
• Both condensins and Cohesins contribute to chromosome segregation during mitosis
• Defects in sister-chromatid cohesion lead to major errors in chromosome segregation in yeast mutants)

Condensin Role

• As the cell enters M phase, condensins bind to sister chromatids along the length of the chromosomes
• Partial removal of cohesins occurs so that only the Cohesins remain only at the centromere
• The sister chromatids remain linked only at centromere region

Mitotic Spindle Formation

• Development of mitotic spindle initiates at prophase
• Centrosomes (duplicated during S phase) separate and move to opposite sites of the nucleus and undergo maturation, becoming the poles the mitotic spindle.

Microtubule Role

• Number of microtubules emanating from the centrosomes increases
• Long interphase microtubules are converted into large numbers of short microtubules radiating from the centrosomes
• At the end of prophase, the breakdown of the nuclear envelope allows some of the spindle microtubules to attach to kinetochores of chromosomes to initiate chromosome prometaphase movement.
• Proteins such as microtubule motors direct movement of chromosomes toward the (-) ends of microtubules.

Three Classes of Microtubules of the Mitotic Spindle in an Animal Cell

• Kinetochorial microtubules: attach to kinetchores of the chromosomes
• Interpolar microtubules protrude from two poles and interdigitate at the spindle equator
• Astral microtubules radiate out from the poles into the cytoplasm and contract with the cell cortex.
• Plus ends of the microtubules project away from the centrosomes, and the minus ends are anchored at the spindle poles.

Animal Cell vs Plant Cell Cytokinesis

• Animal cells - the plasma membrane is pulled inwards around the equator of the cell to form a cleavage furrow by contractile proteins that contract create the furrow. As it reaches its center, the center of the cell, the cell becomes pinched, therefore results in two independent daughter calls.
• Plant cells - divide by forming new cell walls and plasma membranes inside the cells during early telophase. Golgi vesicles carrying the cell precursors accumulate at the metaphase plate and fuse to form a disc-like structure or cell plate, and then the cell plate expands outward and fuses with the plasma membrane to divide the cytoplasm..