The cell cycle Flashcards
What is the purpos of the cell cycle?
duplication of cell contents (DNA, organelles and cytoplasm)
division into new daughter cells
how many organisms does the cell cycle give rise to in unicellular organsims?
2
purpose of the cell cycle in multicellular organisms
A zygote must undergo many rounds of the cell cycle to make a new fully grown organism
Must also constantly replace any cells that die during the lifetime of the organism
cells which are in G0 and cannot re enter the cell cycle
Nerve cells cell cycle re-entry is not possible
Hepatocytes are maintained in G0 unless stimulated to divide Epithelial cells and haematopoietic cells in the bone marrow are constantly in the cell cycle
DNA contents during cell cycle
FACS analysis allows us to see that DNA content is greatest during G1 phase and the lowest during the S phase
stages of interphase and mitosis
G1 = growth and preparation for S phase
S = chromosome duplication
G2 = Growth and preparation for M phase
Interphase = G1+S+G2
M = mitosis+cytokinesis
mitosis
Prophase:
Chromosomes condense
Centrosomes move to opposite poles
Mitotic spindles form
Prometaphase: Nuclear envelope breakdown Chromosomes attach to the mitotic spindle Metaphase: Centrosomes are at opposite poles Chromosomes are at there most condensed and line up at the equator of mitotic spindle Anaphase: Sister chromatids separate Each new daughter chromosome move to opposite spindle pole Telophase: Chromosomes arrive at the spindle fibres These chromosomes expand Nuclear envelope forms Cytokinesis Cytoplasm divides
mitotic spindle
Bipolar array of microtubules
Start assembling during prophase from the centrosomes at each pole Attach to the chromosmes via the kinetochore Pull apart the sister chromatids 3 types of spindle fibres: Astral microtubules Kinetochore microtubules interpolar microtubules
kinetochore
a protein structure formed on a chromatid, where the spindle fibres attach and pull the chromatids apart during cell division
centromere
a part of the chromosome connected to the spindle fibre
chromatids
the two chromosomes that have been replicated and linked through the centromere
Centrosome cycle
Microtubule organizing centre in somatic animal cells
Centrosomes consists of a pair of centrioles surrounded by pericentriolar matrix Duplicated during interphase Migrate to opposite poles in preparation for M phase
Cytokinesis
Final step of the cell cycle
Divides the cytoplasm into two daughter cells Contractile ring: Cytoskeletal structure composed of actin and myosin bundles Accumulate between the poles of the mitotic spindle beneath the plasma membrane Ring contracts and forms an identation or cleavage furrow, dividing the cell in two
Cell organelle division
The cell organelles must be redistributed between the 2 new daughter cells
Cell organelles spontaneously regenerate so must be already present in the new daughter cells
Mitosis vs meiosis
Mitosis:
Two cells Diploid Cell divides once No recombination between homologous chromosomes Meiosis: Four cells Haploid Cell divide twice Homologous recombination occurs
Meiosis
Division which starts with one diploid cell and ends with 4 haploid cells
Produces sperm and egg cells First there’s a round of DNA replication during the S phase to double the genetic content Meiosis one: Homologous chromosomes line up on the spindle and then separate to opposite spindle poles Meiosis two: Sister chromatids line up on the spindle and separate to opposite spindle pole Recombination occurs between homologous chromosomes
Nondisjunction
Failure of homologous chromosomes to separate from one another either at meiotic division one or meiotic division two
If in autosomes, usually fatal however there are a few exceptions: Trisomy 21 (downs syndrome) Sex chromosomes: XO (turners syndrome)
Regulation of the cell cycle:
Entry into the cell cycle must be strictly controlled Each phase must only occur only once per cycle Phases must be in the correct order and non overlapping
Checkpoints in the cell cycle (G1 checkpoint)
Check extracellular environment, growth factors, mitogenic signals and check for DNA for damage
Induction/ expression of cyclin D Binding/ activation of Cdk4 Phosphorylation of pRB Release and activation of E2F S phase gene transcription DNA Damage repair: Normal p53 degrades very quickly, is unstable and maintained at very low levels Phosphorylated p53 is not degraded Active p53 promotes the transcription of the p21 gene that induce cell cycle arrest which gives more time to repair damaged DNA
Checkpoints in the cell cycle (G2 checkpoint)
Check DNA replicated properly, check for DNA damage
Checkpoints in the cell cycle (metaphase checkpoint)
Are all chromosomes aligned on the mitotic spindle
Cell cycle regulators
Cdks
Enzymes which phosphorylate the target proteins
Become active when bound to a corresponding cyclin
Cyclins Regulators of Cdks Different cyclins are produced at each phase of the cell cycle
Cell cycle control
Cdk levels fairly stable throughout the cell cycle
Cyclin levels vary as part of the cell cycle Cdk bound to cyclin is active and can phosphorylate target protein Cdk activation triggers the next step in the cell cycle such as entry into S phase or M phase Cyclin degradation terminates Cdk activity
Cyclin-dependant kinase inhibitors
INK4
Inhibit G1 CDK’s CDK inhibitory protein Inhibit all other CDK-cyclin complexes gradually sequestered by G1 CDKs thus allowing activation of later CDKs
