Cell Division Cycle and Phases

The Cell-Division Cycle

• Cells replicate their contents then split in two
• This cycle is how all living things propagate
• Unicellular species produce an additional organism with each cell division
• Multicellular species need cell division to create a new individual and replace old cells
• Requirements are universal, however details may vary
• DNA must be faithfully replicated to produce two identical daughter cells
• Replicated chromosomes must be segregated into two separate cells
• Most cells double in mass and duplicate cytoplasmic organelles in each cycle
• Complex processes must be coordinated during the cell cycle

Phases of the Eukaryotic Cell Cycle

• The cell cycle has successive phases, including Interphase
• Followed by G1 phase (Gap 1):
  • The cell grows and synthesizes proteins and organelles
  • Prepares for DNA replication
  • Includes the G₁/S checkpoint to ensure readiness for the next phase
• S phase (Synthesis):
  • DNA replication occurs, creating two identical copies of each chromosome
  • In animal cells, centrosomes duplicate
• G2 phase (Gap 2):
  • Further cell growth and protein production for mitosis
  • Cell checks for DNA replication errors and repairs them
  • Followed by G2/M checkpoint, ensuring readiness to proceed to mitosis
• M Phase:
  • Mitosis: Duplicated chromosomes separate into two identical sets, forming two new nuclei
  • Cytokinesis: Cell divides into two daughter cells
• During interphase, the cell grows continuously, while during M phase it divides
• DNA replication occurs only during S phase
• G1 phase is the gap between M phase and S phase
• G2 phase is the gap between S phase and M phase
• Cells in G1 (if uncommitted to DNA replication) can enter a resting state called G0 (G zero)
  • In G0 cells remain for days, weeks, or years before resuming proliferation

Checkpoints and Cell-Cycle Control System

• The cell-cycle control system relies on cyclin-dependent protein kinases (Cdk)
  • Cdks induce downstream processes by phosphorylating proteins on serines and threonines
  • Cyclins bind to Cdk molecules, controlling their ability to phosphorylate target proteins
  • Cyclins called so because they undergo synthesis and degradation in each cycle
  • Mitotic cyclins bind to Cdk molecules during G2 and entry into mitosis
  • G1 cyclins bind to Cdk molecules during G1 and are required for entry into S phase
• Events that move the cell into mitosis:
  • Mitotic cyclin gradually builds up during G2
  • Binds to Cdk to form M-phase-promoting factor (MPF)
  • Enzymes activate MPF through phosphorylation and dephosphorylation
  • Activated MPF is short-lived
  • Mitotic cyclin degradation causes MPF to be rapidly inactivated
  • This occurs at the metaphase-anaphase boundary, enabling cell exit from mitosis

Quality Control Checkpoints

• G₁/S checkpoint: Cdk regulated by inhibitory proteins:
  • Active cyclin-Cdk complexes promote cell cycle progression
  • Cdk inhibitors negatively regulate cyclin-Cdk complexes
  • This prevents premature progression through the G₁/S checkpoint
• G2/M checkpoint: Needs M-Cdk to be active:
  • M-Cdk drives the cell from G2 phase into M phase
  • M cyclin binds to M Cdk, forming the inactive M-Cdk complex
  • Wee1 kinase adds inhibitory phosphates to Cdk1, keeping it inactive
  • Cdc25 phosphatase removes these inhibitory phosphates, activating M-Cdk
  • DNA damage keeps Cdc25 inactive and stops proceeding to M-phase
• Metaphase checkpoint:
  • Triggers: Cyclin proteolysis and is induced by Anaphase Promoting Factor (APC)
• APC is activated once all chromosomes are properly aligned

Cohesins and Condensins

• Chromosome condensation is needed for chromosome segregation into daughter cells
  • Condensation is accompanied by histone H1 molecule phosphorylation
• Phosphorylation of histone H1 by MPF may cause chromosome condensation at M phase onset
• Cohesins tie together sister chromatids in each duplicated chromosome
  • Seem to form large protein rings that prevent chromatids from separating until mitosis
• Condensin helps coil each sister chromatid into a compact structure for segregation during mitosis

Cytoskeleton in M Phase

• Chromosome condensation leads to (1) mitosis (chromosome segregation and formation of two nuclei),
• and (2) cytokinesis (splitting of the cell in two)
• Two structures carry out these processes:
  • A bipolar mitotic spindle forms composed of microtubules and their proteins
    • Bipolar spindle aligns replicated chromosomes in a plane bisecting the cell
    • Each chromosome separates into daughter chromosomes, moved to opposite poles by the spindle
  • A contractile ring of actin filaments and myosin-II appears in animal cells
    • Ring forms under the plasma membrane, perpendicular to the spindle axis
    • Ring pulls the membrane inward, dividing the cell and ensuring each daughter cell has constituents
• Cytoskeletal structures can form independently in specialized cells
• Formation is closely coordinated, so cytoplasmic division (cytokinesis) occurs after nuclear division

Mitosis Events

• Prophase:
  • Chromatin condenses into well-defined chromosomes
  • Each chromosome duplicates during S phase, existing as two sister chromatids
  • These contains a centromere, needed for proper segregation.
  • At the end of prophase, cytoplasmic microtubules disassemble
• Prometaphase:
  • Marked by nuclear envelope disruption
  • Specialized protein complexes (kinetochores) start mature on each centromere and attach spindle microtubules
  • Kinetochore microtubules cause agitation in chromosomes
• Metaphase:
  • Kinetochore microtubules align chromosomes halfway across the spindle poles
  • Chromosomes are held in tension at the metaphase plate by microtubules attached to opposite poles
• Anaphase:
  • Anaphase begins with separation and the microtubules shorten at the chromosomes
  • The spindle poles move farther apart
• Telophase:
  • Separated chromosomes arrive at the poles and the kinetochore microtubules disappear
  • New nucelar envelope formed
• Cytokinesis:
  • Begins during anaphase
  • Membrane around the middle of the cell around to form a cleavage furrow

Sexual Life Cycle

• Involves alternating between haploid and diploid stages
  • Meiosis produces haploid gametes
  • Fertilization fuses them to form a diploid zygote
  • Zygote undergoes mitosis to develop into a multicellular organism
• Haploid are cells with a single set of chromosomes (n)
• Diploid are cells with two sets of chromosomes (2n)
• Meiosis reduces the number of chromosomes in half, producing haploid gametes
• Fertilization: The fusion of two haploid gametes (sperm and egg) to form a diploid zygote
• Zygote's Development: The zygote undergoes mitosis and differentiation to develop into a multicellular organism
• Animals, including humans, have diploid-dominant
• Fungi and some algae have haploid-dominant
• Plants and some algae alternate between the multicellular diploid and haploid

Meiosis and Genetic Diversity

• A diploid nucleus has twoversions of each chromosome (except sex chromosomes)
  • Version from the male parent (paternal chromosome)
  • Version from the female parent (maternal chromosome)
  • The two versions are called homologues, maintaining completely separate existence
• When each chromosome is duplicated by DNA replication, at first the twin copies = sister chromatids
• Sister chromatids line up on the spindle during mitosis with the kinetochore fibers
• During anaphase the sister chromatids then separate from each other to form as individual chromosomes
• During gamete production via diploid cell division
  • Must contain half the original number of chromosomes
  • Homologues recognize each other and become physically paired
  • Each chromosome replicates, making two sister chromatids
  • Unit then pairs with its partner, forming a bivalent, containing four chromatids
  • Genetic recombination occurs, exchanges occur within maternal chromatids
  • The bivalents line up on the spindle
  • During anaphase each pole receives two homologues
• Meiosis consists of two cell divisions with initial DNA replication
  • Four haploid cells are produced from each initial cell
• Meiosis I and II have major differences compared to mitosis
• Prophase I Sub Stages: Leptotene, Zygotene, Pachytene, Diplotene, and Diakinesis
  • Leptotene: Chromosomes become visible as thin threads
  • Zygotene: Homologous chromosomes pair up and synapsis begins
  • Pachytene: Synapsis is completed, and crossing over occurs
  • Diplotene: Homologous chromosomes begin to separate but remain attached at chiasmata
  • Diakinesis: Chromosomes condense further, and the nuclear envelope breaks down

Genetic Reassortment

• Involves the random distribution of maternal and paternal homologues from meiotic division I
• Leads to multiple unique gamete combinations
• Chromosomal crossing-over occurs
  • It takes place during the long prophase of meiotic division I, in which parts of homologous chromosomes are exchanged
  • This process scrambles the genetic structure of gametes
• Crossover involves 2 chromosomes exchanging fragments between nonsister chromatids by general recombination
• Cytologically, crossovers are called a chiasma

Synaptonemal Complex

• Helps the exchange of genetic material between chromosomes during meiosis
• Involved during the phase I of meiosis
• It has two elements, with a central regions that resemble railroad tracks
• Helps in transverse filament assembly
• Prevents breaks from entering combination pathways

Mendel's Laws of Inheritance

• Traits are inherited discretely
• There inherited as discrete units like different colored marbles
• The same gene can have versions

Alleles

• Arise for every gene: An allele is any alternative form of a gene
• Genetic makeup of a gene
• Phenotype is the result of the physical characteristics of individual
• Homozygous (purebred) describes two alleles that are the same
• Heterozygous (Hybrid) describes two alleles that are different
• Alleles can be represented using letters
• Dominant Alleles are represented are represented by uppercase letters
• Recessive Alleles represented in lowercase letters

Laws of Segregation

• Traits are inherited as discrete units
• Organisms inherit 2 copies of each gene, inherited from both parents
• The 2 copies segregate during gamete formation
• Last 2 statements are the law of segregation