21.1: Overview of the Cell Cycle and Its Control

• Phases of the cell cycles:

  • M (mitosis)

  • G1 (between mitosis and DNA replication initiation

  • S (DNA replication)

  • G2 (between DNA replication completion and mitosis)

• Cyclin-CDK complexes regulate the progress of a cell through the cell cycle and are made up of a regulatory cyclin subunit along with a cyclin-dependent kinase subunit

• Chromosomal condensation and the disassembly of G1 and G2 cells nuclear envelope is caused by discussible cyclin CDK

• Yeast cell division isolation mutants help with identifying genes that help regulate the cell cycle

• Eggs and early embryos of amphibians and invertebrates when fertilized provide extract sources that help in biochemical studies for the cell cycles events

21.2: Biochemical Studies with Oocytes, Eggs and Early Embryos

• Mitotic cyclin activity is needed for protein kinase MPF

• MPF activity in the cells as they enter mitosis increases along with the concentration of mitotic cyclins

• MPF activities rise and fall is result by concomitant synthesis and mitotic cycle degradation

• Ubiquitin ligase activity of the APC is controlled so the late anaphase is the only time that mitotic cyclins are polyubiquitinated and not before

21.3: Genetic Studies with S. pombe

• The fission yeast S. pombe gets encoded a cyclin-dependent protein kinase which is associated with a mitotic cyclin, which results in a mitotic cyclin CDK heterodimer

• Two residues in the catalytic CDK subunit being at a certain phosphorylation state affects protein kinase activity of the cyclin CDK complex

• The onset of mitosis is affected by an actuated mitotic cyclin CDK complex, which is dependent on a decrease of Wee1 and an increase of Cdc25

• S. pombe MPF and human cyclin A-CDK2 complex are similar to each other

21.4: Molecular Mechanisms for Regulating Mitotic Events

• MPF catalyzed phosphorylation of lamins A, B, and C along with inner nuclear proteins and nucleoporins occurs early in mitosis

• Kinase regulates the phosphorylation of condensin complexes powered by MPF

• DNA replication in the S phase forms sister chromatids that are linked at the centromere because of cohesion complexes

• Cdc20 directs APC to polyubiquitinated securin at the onset of anaphase

• The APC polyubiquitinated mitotic cyclins with the direction of Cdh1 after sister chromatids move to spindle pores

• Protein phosphates are able to remove regulatory phosphates such as:

  • Condensin

  • Lamins

  • Nucleoporins

• They are able to do this when MPF activity falls

• MPF activity falling also helps with the removal of inhibition of the myosin light chain, which lets the cleavage furrow form into cytokinesis

21.5: Genetic Studies with S. cerevisiae

• The single cyclin-dependent kinase (CDK) which is encoded by CDC28 is expressed by S. cerevisiae

• The three cyclins active in G1:

  • Cln1

  • Cln2

  • Cln3

• Heterodimers are formed with CDK when Clb3 and Clb4 are expressed during the S phase

• DNA replication takes place at certain origins only once until a cell goes through anaphase

21.6: Cell Cycle Control in Mammalian Cells

• Mitogens which are peptide growth factors make mammalian cells that are cultured proliferate

• This helps guide cells into the S phase, G2 phase, and mitosis even without growth factors present

• Mammalian cells regulation requires CDKs and cyclins

• Cyclin CDK complexes are regulated phosphorylation and dephosphorylation in mammalian cells

21.7: Checkpoints in Cell Cycle Regulation

• The endurance that chromosomes are intact in cells and that the cell cycle is progressing properly is given by checkpoint controls

• Unreplicated DNA checkpoint

• During S and G1

• Prevent MPF before the synthesization of DNA

• Activates CDK1 and Cdc25c

• Spindle assembly checkpoint:

• Prevents premature anaphase

• Uses Mad2 and other proteins for the regulation of APC

• Chromosome segregation checkpoint

• Makes sure telophase and cytokinesis occur after daughter cells have been segregated

• Allows for daughter cells to have a full set of chromosomes

• DNA damage checkpoint

• Arrests cell until DNA damage is fixed if any DNA damage occurs

• Three tumor suppressor proteins are needed here:

  • ATM/ATR

  • Chk1

  • p53

21.8: Meiosis: A Special Type of Cell Division

• One cycle of chromosome replication and two cycles of cell division are needed in meiosis for the production of haploid germ cells

• Chromatids and homologous chromosomes have at least one recombination occur between them

• Cell cycle proteins that work in mitotically dividing cells also work in meiosis undergoing cells