Ch 12: The Cell Cycle

Asexual Reproduction

cell divides through binary fission to create a copy of itself

• daughter is genetically identical to parent

• prokaryotes, protists (ex. amoeba)

Mitosis: Eukaryotic Cell Division

• equal division of genetic material in nucleus (DNA) and organelles in cytoplasm between two cells

• daughter cell is genetically identical to parent

• used for tissue repair and growth

Cell contain almost 2m of DNA

• double stranded DNA wraps around protein histone to form nucleosome

• further condensed to chromatin (cylindrical fibers) then condensed to individual chromosomes

• each chromosome contains hundreds of genes

• every species has specific number of chromosomes in nucleus

Humans have this amount of chromosomes

46 chromosomes

• 23 pairs

Dogs have this many chromosomes

78 chromosomes

• 39 pairs

Atlas Blue Butterfly have this many chromosomes

448 chromosomes

• 224 pairs

Gevy Zebra have this many chromosomes

46 chromosomes

• 23 pairs

DNA and Chromosomes

• DNA carries hereditary information (genes)

• double-stranded polymer of nucleotide monomers

  • anti-parallel and complementary

• DNA is organized into units called chromosomes

  • prokaryotes have one circular chromosome

  • eukaryotes have multiple, linear chromosomes

Eukaryotic Chromosome Structure

Centromere: the “waist” of the chromosome

• where kinetochore attaches

Chromosome Arms: one above, one below centromere

Telomere: protective “caps” at both ends of chromosome

Chromosomes

• number of chromosomes not correlated to intelligence, complexity, etc

• sometimes unrelated species hav same number of chromosomes

• closely related species have similar chromosomal numbers

Chimpanzees have this amount of chromosomes

48 chromosomes

• 24 pairs

Horses have this many chromosomes

64 chromosomes

• 32 pairs

Donkeys have this many chromosomes

62 chromosomes

• 31 pairs

Homologous Chromosomes (homologs)

• eukaryotic cells have two copies of each chromosome

  • one from mom, one from dad = homologous pair

• homologs: contain same gene character but may have different traits

Human Karyotype

• karyotype displays homologous chromosomes arranged by size

• 46 chromosomes; 23 pairs (1 chromosome from mom, 1 from dad)

• pairs 1-22 are autosomes, don’t determine sex of offspring

• 23^rd pair are sex chromosomes, X and Y

  • females XX

  • Males XY

Somatic Cells

• body cells: skin cells, liver cells, brain cells, etc

• diploid (2n): number of chromosomes in somatic cells

  • each cell contains both copies of each chromosomes

Gametes

• egg and sperm

• haploid (n)

Cells

• need to divide for growth and repair

• one cell gives rise to other cells

• cell divides DNA, organelles, plasma membrane, etc.

• it’s important to divide DNA properly

Interphase

• longest phase of cell cycle

• when cell needs to divide, it begins getting ready to interp

  • DNA is replicated during this phase

    • need 2x the DNA

  • additional cytoplasmic components synthesized during this

    • need additional organelles

  • cell grows

    • need extra plasma membrane

• 3 sub-phases: Gap1 phase , S phase, Gap2 phase

Gap 1 Phase

• “first gap”

• growth occurs when cell receives signal to divide

S phase

• “synthesis”

• DNA is replicated (synthesized)

• centrosome is replicated

Gap 2 phase

• “second gap”

• growth continues

• cell prepares to divide

DNA Synthesis (replication)

• DNA must be replicated prior to cell division

• after DNA synthesis, each chromosome is comprised of two sister chromatids joined together at the centromere

  • cohesion proteins bind them together

Sister Chromatids

• before cell division, chromosomes are copied, creating sister chromatids

• joined together at centromere

• identical to each other

  • the exact DNA sequence is copied during S phase

Mitotic Spindle

• microtubules and associated proteins

• attach to chromosomes at the centromere, and move them during mitosis

• fibers extend from centrosomes to attach to the chromosomes

  • attached to chromosomes at the kinetochore

  • specific location on centromere where proteins bind to facilitate attachment of mitotic spindle

Centrosomes

hub of organization for microtubules

• duplicated during interphase to form two per cell

• migrate to poles of cell

Mitotic Phase

Mitosis

• replicated DNA is divided into two daughter nuclei

• 5 phases: prophase, pro metaphase, metaphase, anaphase, telophase/cytokinesis (nuclear membrane reform, cytoplasm divided, usually shown accompanying telophase)

Prophase

• chromatin begins to condense into discrete chromosomes

  • each replicated chromosome is comprised of two identical sister chromatids

• nucleolus disappears

• mitotic spindle begins to form from centrosomes

• centrosomes begin to move to opposite poles of the cell

Prometaphase

• nuclear envelope (membrane) begins to break down

  • microtubules can now enter nuclear region

• chromosomes condense further

• kinetochores form at the centrosome of each sister chromatid

• microtubules attach to chromosomes at kinetochore

  • called kinetochore microtubules

    • each sister chromatid has a microtubule attached, one from each pole

• non-kinetochore microtubules extend the length of the cell, elongating it

Chromosomes

• DNA is not condensed during interphase

  • cannot see individual chromosomes

• DNA starts to condense during prophase

  • can now see individual chromosomes

Metaphase

• centrosomes are now at opposite poles of the cell

• microtubules have attached to kinetochore of chromosomes

• chromosomes have been pulled to the equator of the cell

  • called metaphase plate

  • sister chromatids line up at metaphase

Anaphase

• cleavage of cohesion proteins holding sister chromatids together

• sister chromatids separate from each other

  • are now separate “daughter” chromosomes

• microtubules shorten

  • pull daughter chromosomes to opposite poles of the cell

• cell elongates

• at end of anaphase, each pole of cell contains identical genetic material

Telophase/Cytokinesis

• nuclear membrane forms around both sets of daughter chromosomes

• nucleolus reforms in each nucleus

• chromosomes are become less condensed

• microtubules are depolymerizing

• mitosis is complete once both nuclear membranes have reformed

• cytokinesis is division of cytoplasm into two separate cells

  • cleavage furrows forms

    • ring of microtubules which contrast

    • pinch towards center of cytoplasm to form two daughter cells

Cell Cycle Control (NOT FINISHED)

• cell division/replication varies between different cell types

  • skin cells divide often

  • most somatic cells divide only when necessary

  • nerve cells never divide

• differences are due to molecular regulatory differences

  • a cell should go through mitosis

  • if there’s an error along the way,

  • a cell knows when to stop dividing

(Internal) Molecular Checkpoints

• cells have three main checkpoints within the cell cycle

  • Gap 1, Gap 2, Mitosis

• each checkpoint has “stop” and “go” signals that regulate cell cycle

Gap 1 Checkpoint

“restriction point”

• checks for: growth factors, DNA damage, cell size, nutrients

• crucial checkpoint for mammals

• “go” signal: cell continues to S phase and into Gap 2 phase

• “stop” signal: cell moves into a non-dividing state if necessary

  • injury

Cyclins

• type of regulatory molecules

• protein

• concentration fluctuates throughout cell cycle

Kinases

• type of regulatory molecules

• enzymes

• activate other proteins by phosphorylating them

• concentration is consistent throughout cell cycle

  • mostly in inactive form

  • to be activated they must be attached to a cyclin

    • cyclin-dependent kinases (CDK)

  • activity of CDKs rises and falls along with cyclin concentration

Gap 2 Checkpoint

• mitosis promoting factor

  • CDK + cyclin = MPF

    • when active, gives “go” signal for cell to go from Gap 2 to Mitosis

    • is active when cyclin levels are high

    • cyclin is produced late in S phase and in Gap 2

      • checks for DNS damage & proper DNA replication

    • inactive when cyclin levels are low

  • when MPF concentration is high, cell passes G2 checkpoint and begins mitosis

    • MPF activity is highest during metaphase

    • during anaphase, cyclin begins to degrade. without cyclin there is not MPF

      • this triggers the cell to end mitosis

M Phase Checkpoint

• checkpoint during Metaphase of Mitosis

  • checks that all chromosome kinetochores are attached to a microtubule spindle fiber

• “go” signal: cell proceeds through anaphase to telophase

  • cell can attempt to attach kinetochores correctly

  • if it can’t, cell will eventually die

Cell Cycle Controls: External Factors

• density-dependent inhibition

  • cells stop growing when they get too crowded

    • ex. woulds stop growing when healed

• anchorage-dependence

  • to complete mitosis, cell must attach to substrate such as another cell or tissue matrix

Cell Cycle Controls and Cancer

• cancer cells don’t fallow normal cell cycle signals

  • DNA damaged → genes damaged

• cancer cells grow & divide abnormally & uncontrollably

  • failure of at least one of 3 internal checkpoints (G1, G2, M)

  • results in unregulated growth

• cancer cells can go through mitosis without being attached to another cell or tissue

  • failure of anchorage-dependence

    • can continue to divide without proper attachment

  • results in cancer cells spreading to other tissues (metastasis)