BI 220: Apoptosis and Cell Reproduction

Prophase

First stage of mitosis; chromosomes condense, centrosomes begin to separate, cell starts to build the mitotic spindle

Prometaphase

Nuclear membrane breaks down, kinetechores form on the centromic DNA, microtubules begin to make attatchments to the chromosomes

Metaphase

Chromosomes align at the metaphase plate, each chromosomes should be bioriented under tension

Anaphase

Cohesion is cleaved, microtubules will pull sister chromatids apart, centrosome separate

Telophase

Spindle disassemble, chromosomes decondense, reform the nuclear envelope

Cytokinesis

Division of cytoplasm, forms two daughter cells.

Centrosome

Organizes microtubules during cell division, the complex of tubulin proteins from which the mitotic spindle grows

Kinetochore

Protein structure on chromosomes for spindle attachment.

Cohesin

Protein that holds sister chromatids together.

Microtubules

Cytoskeletal fibers that pull chromosomes apart.

RhoA

GTPase critical for cytokinesis and contractile ring formation.

Phragmoplast

Structure for cell plate assembly in late cytokinesis in plants.

Checkpoints

Regulatory points in the cell cycle.

G1 Checkpoint

Checks for DNA damage before S phase.

G2 Checkpoint

Ensures DNA replication is complete before mitosis.

M Phase Checkpoint

Verifies spindle attachment before anaphase, cell spends 10% of its time here

p53 Protein

Tumor suppressor protein that stop cell division at specific checkpoints if there is a problem

Cyclin

Regulatory protein that activates cyclin-dependent kinases.

Cdk

Cyclin-dependent kinase; regulates cell cycle progression.

pRb

Retinoblastoma protein; inhibits cell cycle progression.

Apoptosis

Programmed cell death; eliminates damaged cells.

Sister Chromatids

Identical copies of a chromosome joined at centromere.

Chromatin

DNA and protein complex; condenses to form chromosomes.

Centromere

Region where sister chromatids are joined.

Nuclear Envelope

Membrane surrounding the nucleus; breaks down in mitosis.

Histones

Proteins that package and order DNA into structural units.

Interphase

Phase where the cell grows and DNA is replicated, cells spend most of their time here (90%)

G1 Phase

First gap phase; cell grows and synthesizes proteins.

S Phase

Synthesis phase; DNA is replicated, creating identical copies of each chromosome

G2 Phase

Second gap phase; cell prepares for mitosis.

Cell Cycle

Series of phases that cells go through for division.

Organism growth, replacement of lost or damaged cells, organism reproduction

Why do cells reproduce?

Extracellular molecules (growth factors/mitogens), GF-receptor binding triggers multistep signal transduction relay, results in molecular changes that stimulate (or inhibit) cell reproduction

What signals cell reproduction?

Ras-MAP kinase pathway

Many growth factors signal through RTKs to activate the ___.

Duplication of DNA (chromatin changes, chromosome duplication), growth of cell in size, segregation of DNA (chromosome movement, nuclear division in eukaryotes), cytoplasmic division

During reproduction, all cells must accomplish four things...

Binary fission

Asexual reproduction used by prokaryotes

Mitotic divison

Asexual reproduction used by eukaryotes

Sexual reproduction

Meiotic division (+ fertilization), often used for organism reproduction in eukaryotes

During chromosome replication

When does the cell elongate in binary fission (prokaryotes)?

Circular DNA molecule

Single bacterial chromosome

An identical complete genome

In binary fission (prokaryotes), each daughter cell inherits ___.

Nuclear membrane, genome on multiple chromosomes, growth & DNA replication as separate steps

Differences between prokaryotic and eukaryotic cell division: Eukaryotic cells have...

Tension, microtubules

The goal of the kinetochore attaching chromosomes to the spindle is to create ___ across the kinetochore due to pulling forces from ___ attached to the two spindle poles.

Closer to the spindle poles

Microtubules shorten at the kinetochore end to pull chromosomes ___.

Contractile ring

Cytokinesis is accomplished by constriction of a ___ - form the furrow..

GEF

Guanine nucleotide exchange factors that causes a protein to lose a GDP and replace it with a GTP

GAP

GTPase activating protein

Cytokinesis

Defects in Rho signaling lead to ___ failure.

+

Kinesine motors move Golgi vesicle to (___) ends of microtubules.

Cell plate

Fusion of Golgi vesicles forms ___ (growing wall sandwiched between two membranes)

Growing edges of cell plate

Phragmoplast expands in diameter, so microtubules lined up with ___.

Regulated

Cell reproduction is a highly ___ process.

G1

Rb inhibits TFs that promote progression into ___.

G1, G2

Kinases often give "go ahead" signal at ___ & ___ checkpoints.

Cdk/cyclin

What regulated Rb?

Rb

Regulates cell cycle progression by controlling the transition from G1 to S phase

Cdks (drive the cycle forward by phosphorylating substrates when bound to cyclins), ubiquitins (regulate cyclin degradation, which is how cells rapidly drop cyclin levels to exit a phase or reset)

What enzymes control the rapid changes in levels of the cyclins to promote cell cycle progression?

Pause & repair or apoptosis

What happens if a problem is detected at a checkpoint?

16, 16

A group of cells is assayed for DNA content immediately following mitosis and is found to have an average of 8 picograms of DNA per nucleus. Those cells would have ___ picograms at the end of the S phase and ___ picograms at the end of G2.

20

If there are 40 chromatids in a cell at metaphase, how many chromosomes are there in each daughter cell following cytokinesis?

Mitogens

Promote cell division

Growth factors

Promote cell size increase

Survival factors

Surpress apoptosis

Development, tissue homeostasis, injury/disease

When do cells die?

Apoptosis, necrosis, autophagy, etc.

How do cells die?

Autophagy

A lysosome-mediated pathway for organelle degradation

Genetically programmed, starvation-induced, aids in organelle turnover, cell death (sometimes)

Autophagy is...

Cell shrinkage; chromatin condense then fragment, nuclei bleb; plasma membrane blebs to form apoptotic bodies; engulfment & destruction by phagocytes (recognize exposed phosphatidyl serine)

Apoptosis morphological hallmarks

Caspase protease

The executioner of apoptosis, which are activated by cleavage

Inactive precursors, active, irreversible

Procaspase are ___. Caspase are ___. Caspace activation is ___.

Cleave, activate

Initiator caspases ___ and ___ executioner caspases, which can further amplify the signal or directly target degradation of cellular structures.

Signal amplification

The caspase activation cascade is an example of ___.

Intrinsic, extrinsic

Apoptosis can be induced by ___ or ___ death signals.

Radiation, toxins, hypoxia, DNA damage, loss of growth factors, etc/

Intrinsic death signal triggers

Leads to mitochondrial permeability through Bax & Bcl2 can antagonize this activity

Intrinsic death signals

Death ligands and receptors

Extrinsic death signals triggers

Bcl2, mitochondrial permeability

The intrinsic apoptosis pathway is regulated by ___ family members and ___.

Prodeath, prodeath, prosurvival

Bax is ___. Bak is ___. Bcl2 is ___. (prodeath or prosurvival)

Prosurvival, prodeath → cytochrome c release from mitochondria → apoptosome formation initiates caspase activation

Intrinsic apoptosis pathway steps

Normal developmental, pathologic

Apoptosis occurs during ___ processes, whereas necrosis is ___.

Necrosis

Tissue death that causes inflammation (harmful)