Cell Cycle Regulation & Meiosis

• Why might it be important to regulate the Cell Cycle?

  1. To respond to dynamic needs for growth, repair, and maintenance of tissues
• Why might it be important to regulate the Cell Cycle?

  2. Ensure cell is prepared and “healthy ”enough to proceed to each next stage
• Why might it be important to regulate theCell Cycle?

  3. Unregulated cell division can lead to tumor formation and cancer
• The Cell Cycle is controlled at different stages by proteins that appear and disappear in a cyclical fashion
• Cyclins: Proteins that activate enzymes called cyclin-dependent kinases (CDKs)

  • Appear and disappear throughout the cell cycle
• Active CDKs promote cell division and progression through the stages of the cell cycle

  • Are present throughout the cell cycle but only activated in presence of cyclin
• CDK/Cyclin interactions regulate the timing and progression of cell cycle
• Cyclin/CDK activity: progression through the cell cycle – is regulated by several checkpoints
• If cell doesn’t pass a checkpoint, the cell cycle can be paused and/or apoptosis (cell death) can be triggered
• 3 major checkpoints in the cell cycle:

  1. DNA damage checkpoint
  2. DNA replication checkpoint
  3. Spindle assembly checkpoin
• DNA damage checkpoint regulation by p53

  • When DNA is damaged, p53 gets phosphorylated (activated)
• If DNA damage is irreparable, the cell will undergo apoptosis to prevent it from producing damaged daughter cells
• If DNA is not repaired quickly, p53 will start stimulating the over-production of the “pro- apoptosis” regulator Bax
• Bax competes with “anti-apoptosis” protein Bcl2.
• Normally Bax and Bcl2 are expressed at similar levels, in which case Bcl2 neutralizes Bax by forming a dimer with it
• When p53 overexpresses Bax, Bcl2 is outcompeted and Bax/Bax dimers form, leading to apoptosis
• Cancer: A Disease of Cell Cycle Dysregulation

  • A family of genes known as proto-oncogenes perform various functions in normal cell processes, including growth and division. They are characterized by having the potential to become cancerous if mutated
• Cancer: A Disease of Cell Cycle Dysregulation

  • Oncogene: A mutated proto-oncogene, which can cause cancer
• Cancer: A Disease of Cell Cycle Dysregulation

  • Tumor suppressors: Genes that encode proteins whose normal activities inhibit cell division
• Most human cancers develop from the accumulation of multiple mutations in proto-oncogenes and/or tumor suppressor genes
• When multiple oncogenes become overactivated, or tumor suppressors become inactivated, through mutation, cancer will likely develop
• The gradual accumulation of mutations in multiple oncogenes and tumor suppressor genes over years can turn cancer from benign (slow moving, non-invasive) to malignant (aggressively growing and metastasizing)
• MITOSIS

  Biological situation:

  • Embryonic development

  • Wound healing/wear and tear

  • Regeneration
• Germ cells initially undergo mitosis to make more of themselves
• MEIOSIS

  Biological situation:

  Diploid germ cells undergo meiosis to form haploid gametes (sex cells)
• Mitosis – the division of replicated genome into 2 genetically identical daughter cells
• Mitosis

  • asexual reproduction in single-celled eukaryotes and somatic cells
• Mitosis

  • Includes 1 round of nuclear division.
  • Produces genetical identical, diploid daughter cells
• Meiosis – the formation of gametes(sexual reproduction in multicellular organisms)
• Meiosis

  • Includes 2 rounds of nuclear division.
  • Produces not genetically identicall, haploid gametes (sperm and eggs)
• Mitosis

  • Occurs in all eukaryotes
  • DNA synthesis precedes it
  • One round of cell division
  • Homologous chromosomes never pair up with each other
  • Daughter cells are diploid and genetically identical
• Meiosis

  • Occurs in most eukaryotes
  • DNA synthesis precedes it
  • 2 rounds of cell division
  • Homologous chromosomes pair up
  • Daughter cells are haploid and genetically unique
• Overall goal of meiosis:

  • Diploid germ cells undergo meiosis to form haploid gametes (sex cells)
• First Meiotic division: Homologous chromosomes separate

  Second meiotic division: Sister chromatids separate (like mitosis)
• Prophase I (Meiosis I): Homologous Chromosomes Pair and Crossover

  • Replicated chromosomes condense, homologous chromosomes find each other and pair up (synapsis). Crossing over between non-sister chromatids occurs
• Synapsis: Homologous chromosomes (same set of genes) pair and form a bivalent
• Crossing over: Maternal and paternal chromatids randomly swap DNA segments
• At the end of prophase I, chromosomes are crossed over, the nuclear envelope has begun to disappear, and the meiotic spindle is forming
• Crossing over increases genetic diversity

  • Each chromosome with recombinant non-sister chromatids is a unique mix of paternal and maternal genes.
• Prometaphase 1 and Metaphase I: Further increases genetic diversity

  • Crossing over has occurred and the chiasmata (crossed pieces on each chromosome) are present.
  • The random orientation of homologous pairs increases genetic diversity