cell division

intro

  • most multicellular life begins as a single fertilized egg called a zygote

    • huge ahh cell

  • cell div is key to developing into more complex, multicellular organisms and growing/maintaining adult cell types

  • biologically tightly regulated

    • failure of this regulation can be deadly


the cell’s genome

  • the duplication of a cell’s DNA is central to cell division

    • nearly all somatic cells in the body have identical versions of this code

  • a genome is the full collection of an organism’s DNA

    • the genome is present in nearly all cell in a multicellular animal

  • packed into several large, liner double-stranded DNA molecules called chromosomes

    • humans have 23 pairs of chromosomes (46 total)


genome structure

  • the length of the entire human genome is abt 2m

    • 10uM

  • dna is tightly packed into chromosomes esp during cell division


cell cycle

  • the cell cycle is an ordered series of events involving cell growth and cell division that produces two new daughter cells

  • precisely timed and carefully regulates

three main phases

 interphase = cell grows, dna is replicated

  • g1 - cell grows and prepares for dna replication

  • s phase - dna is replicated, chromosomes are copied

  • g2 - cell prepares for division and checks DNA for errors

miotic phase = replicated dna and cytoplasmic contents are separated

  • right before mitosis

    • centrosome - organelle that is key to orchestrating mitosis

    • sister chromatids - duplicated and connected chromosomes

  • mitosis

    • duplicated chromosomes are aligned, separated into two new identical cells

    • dna of the cell’s nucleus is split into equal sets of chromosomes

    • majority of the cell divisions in the body involve mitosis

    • goal: make sure that each daughter cell gets a perfect full set of chromosomes

  • MITOSIS PHASES

    • prophase

      • early prophase

        • organize chromosomes during mitosis

        • miotic spindle starts to form

        • chromosomes start to condense

        • nucleolus is gone

      • late prophase (prometaphase)

        • nuclear envelops breaks down

        • chromosomes r fully condensed

        • miotic spindle starts to capture chromosomes

      • SPINDLE ANATOMY

        • centromere - dna region where sister chromatids are tightly joined

        • kinetochore - a protein structure that forms on the centromere of chromosomes.

      • metaphase

        • chromosomes line up at a metaphase plate

        • each chromosome’s kinetochores must attach to microtubules from opposite spindle poles

      • anaphase

        • kinetochore microtubules pull chromosomes toward poles

        • microtubules push poles apart

        • sister chromatids separate from each other and are pulled towards opposite ends of the cell

      • telophase

        • chromosomes start to condense

        • spindle disappears

        • nuclear membrane re-forms

        • nucleolus reappears

        • the cell is nearly done dividing, starts to re-establish its normal structures

cytokinesis = cell is split into identical daughter cells.

  • overlaps with anaphase and telophase

  • forms acting ring and cleavage furrow

  • when complete, fully separates cells


g0 phase

  • not all cells are cycling/not actively dividing

  • some are in a quiescent state, a state of rest

  • this can either be temporary or permanent depending on the cell or cellular environment


internal checkpoints

  • daughter cells must be EXACT duplicates of the parent cell

    • if not they gna make bad kids

  • internal checkpoints at g1, g2, and M phases to prevent continuation of the cell cycle

    • g1 checkpoint - cell reserves, cell size, no dna damage

    • g2 checkpoint - all chromosomes duplicated, dna damage

    • m checkpoint - sister chromatids attached to miotic spindle


positive regulation of the cell cycle

  • the cycling and cyclin-dependent kinases (Cdks) are proteins that positively regulate the cell cycle

  • responsible for the progress if the cell through the various checkpoints

  • “forward momentum”

  • different cyclins are fluctuating at specific points in the cell cycle

  • the cyclin-cdk complex must be phosphorylated to be active and continue the cell cycle.


negative regulation of the cell cycle

  • block the progression of the cell cycle until problems are resolved

  • best studied are retinoblastoma protein, p53, and p21

  • discovered to be damaged or non-functional in cells that had begun to replicate uncontrollably (cancerous)

  • act primarily at the g1 checkppint

  • p53 detects dna damage and stops cell cycle

    • if damage too bad, triggers apoptosis

  • p21 is activated by p53 and blocks Cdk/cyclin activity to enfore the cell cycle to stop

  • Rb prevents S phase entry by blocking growth dactors until enough positive signals lead to its inactivation


cancer

proto-oncogenes

  • genes that code for the positive cell-cycle regulators

  • oncogenes

    • mutated genes that cause cancer

tumor suppressor genes

  • code for negative regulator proteins which when activated can prevent the cell from undergoing uncontrolled division

    • Rb, p53, ps1

  • a cell that carries a mutated form of a negative regulator might not be able to stop the cell cycle

  • mutated p53 genes have been identified in more than 50% of all human tumor cells