Biochem U3L5

what is the cell cycle broadly divided into

interphase, mitosis, cytokinesis

what happens during interphase

growth, DNA synthesis

what happens during mitosis

nuclear division

what happens during cytokinesis

division of cytoplasm

which phase do cells spend most of their lives in

interphase

what is the G1 phase

growth phase and preparation time for DNA synthesis, RNA and protein synthesis, if cell is moving on to S then organelles and intracellular structures are duplicated and cell increases in size

if a cell is mature and no longer actively cycling, what phase are they in

permanently in G1

if a cell is very rapidly dividing, how much time is spent in G1

very little

G0 phase

cells in G1 that are not committed to DNA synthesis

what is a quiescent cell

cells that are not yet committed to entering S phase, quiet/resting cells can re-enter active G1 and progress on to S phase

what is the restriction point

the place or time point within G1 that if crossed, will commit a cell to continuing into DNA synthesis in S phase

S phase

synthesis of nuclear DNA, DNA replication occurs

each of the 46 chromosomes in human cell is copied to form sister chromatid and then are tightly condensed into heterochromatin, 92 chromatids once S phase completed

G2 phase

preparation for nuclear division, ensures DNA synthesis is complete and mistakes are repaired, intracellular molecules assess nuclear integrity

5 phases of mitosis

prophase, prometaphase, metaphase, anaphase, telophase

what does mitosis assure

that each daughter cell will have identical complete functional copies of the parent cell’s genetic material

cytokinesis description

actin microfilament contractile ring contracts and results in cleavage furrow, deepening until opposing edges meet and two separate, identical daughter cells are formed

what two types of cells undergo continuous and rapid turnover

intestinal epithelial cells and hematopoietic cells

quiescent cells and the liver donor

portion of liver from donor is given to recipient, lobes in both individuals double in size and regenerate due to quiescent nature of hepatocytes

senescent cells

cells that permanently remain in G0 due to age or accumulated DNA damage, cannot be stimulated to progress, alive and continue to function but cannot divide

what is an example of a senescent cell

neurons, completed last mitosis and will not continue dividing

two major cell cycle mediators

cyclins and cylin-dependent kinases (CDKs)

what are cyclin-CDKs

complexes of certain cyclins with specific CDKs possessing enzymatic (kinase) activity

G1 phase cyclins

D type cyclins (cyclin D1, D2, and D3) and cyclin E are critical for progression through the restriction point

S phase cyclins

Cyclin E and cyclin A

G2 phase cyclins

cyclin A and B

mitosis phase cyclin

cyclin B

abbreviation for CDKs

D E A B: dead (CDK 4 CDK 6) elephants are (CDK2) bad (CDK1)

concentration and activity of a CDK

concentration stays the same, activity changes when cyclin is present

function of cyclin D and CDK 4 and 6

progression past the restriction point at the G1/S boundary

function of cyclin E, A and CDK 2

initiation of DNA synthesis in early S phase

function of cyclin B and CDK1

transition from G2 to M

checkpoints are in place at critical times in cell cycle to:

monitor completion of critical events and delay progression to next phase if necessary

G1 restriction point

cell needs growth factor stimulation to progress, after restriction point no external stimulation is required to progress through S, G2, and M

what does G2 checkpoint ensure

that mitosis does not begin before DNA is completely and correctly duplicated during S phase

what allows cell cycle progression at inappropriate times

mutated tumor suppressor genes

what types of cells typically have mutations in tumor suppressor genes

cancer cells

what is a retinoblastoma

normal functional Rb protein (pRb) that halts a cell in G1 phase

what are key regulators in G1 phase

pRb and P53

what happens when Rb1 is mutated

eye malignancy, hereditary retinoblastoma, unregulated progression through cell cycle

what does pRb bind to

transcription factor E2F, which prevents entry into S phase through binding

what causes pRb to dissociate from E2F and allow cell to move from G1 to S

phosphorylation by cyclin D-CDK4/6

what does p53 regulate

progression in G1 and apoptosis, regulating cell cycle control genes, arresting cell cycle when DNA is damaged, committing cells to apoptosis when DNA damage is too great

what activates p53

nuclear DNA damage results in phosphorylation, stabilization and activation of p53

what CDK pairs with active p53

p21, which halts cell cycle to allow for DNA repair

what does p53 do if DNA damage is irreparable

trigger apoptosis

if mutation if TP53

p53 cannot cause cell arrest and unregulated cell cycle progression occurs, over 50% of human cancers are p53 mutations

two classes of cyclin dependent kinase inhibitors (CKIs)

INK4 and CIP/KIP

what does INK4 inhibit

d type cyclins from activating CDK4/6

what does CIP/KIP inhibit

CDK2 kinases (p21 is a CIP/KIP), thus halts for repair

when does G2 checkpoint regulation occur

after S phase and before initiation of mitosis

what CDK controls entry into mitosis

CDK1

what happens with a defective G2 checkpoint

cells enter mitosis before repairing DNA and may die after cell division

steps of apoptosis

1. membrane phosphatidylserine moves from inner to outer leaflet

2. membranes remain intact but portions bud off and lose their ability to attach to neighboring cells

3. chromatin condenses in the nucleus

4. cytochrome C is released from the mitochondria

5. apoptotic cells are engulfed by phagocytic cells that bind to phosphatidylserine

6. phagocytic cells release inflammation inhibitors

two processes that cells die by

necrosis, apoptosis

necrosis characteristics

rupturing membrane and inflammation, groups of cells dying, passive pathological process

apoptosis characteristics

individual cells die no membrane rupturing or inflammation, active physiological process

homeostasis of cell division and apoptosis

equilibrium relatively constant between new cells and cell death

what is the sonic hedgehog signaling pathway

regulates homeostasis that sends an anti-apoptotic signal to allow cells to survive. failure to receive the sonic hedgehog signal results in apoptosis. if impaired, survival signal can be sent inappropriately, allowing cells to escape death

biological significance of apoptosis

homeostasis, development, elimination of damaged cells

what binds to p53 to allow cell cycle arrest and apoptosis stimulation

pro-apoptotic protein Bax, which releases cytochrome C from mitochondria

what is the Internal Cell Death Program

p53 induces production of Bax, Bax allows cytochrome C to exit mitochondria and activate Apaf-1, induces formation of apoptosome, activates caspase to cause apoptosis

what is abnormal p53 encoded by

a mutant TP53

what is external initiation of apoptosis

tumor necrosis factor receptors have a “death domain” activates caspases to stimulate fast death, can skip over cytochrome C release and apoptosome

two regulators of apoptosis

caspase family of proteases, Bcl-2 family of proteins

what do caspases degrade

celular proteins, nuclear and cytoplasmic proteins, nuclear lamins

what is the caspase cascade

the sequential proteolytic activation of one caspase during another in an orderly fashion during the initiation of apoptosis

Bcl-2 family

a balance of anti and pro apoptotic members, Bax is a pro-apoptotic member