The Cell Cycle, Mitosis, & Meiosis

The Cell Cycle

Stages of the cell cycle

G₁ S G₂	interphase
M	mitosis

Control of the cell cycle

cyclins

G₁ cyclin (cyclin D)

S-phase cyclins (cyclins E & A)

mitotic cyclins (cyclins B & A)

cyclin-dependent kinases (Cdks)

G₁ Cdk (Cdk4)

S-phase Cdk (Cdk2)

M-phase Cdk (Cdk1)

anaphase-promoting complex (APC/C)

Steps in the cell cycle

G₁ cyclins rise

S-phase promoting factor (SPF) [cyclin A + Cdk2]

destruction of cyclin E

M-phase promoting factor (MPF) [mitotic cyclins + Cdk1]

mitotic metaphase

activation of APC/C

chromatid separation → anaphase

attachment of cyclin B to ubiquitin

initiation of synthesis of G₁ cyclin

degradation of geminin

Role of the centrosome in cell cycle progression

Checkpoints

DNA damage checkpoints

check on completion of S phase

spindle checkpoints

apoptosis

mechanisms

internal signals

Bcl-2 on outer mitochondrial membrane

Bax

release of cytochrome C

Apaf-1 (apoptotic protease activating factor-1)

formation of apoptosomes

activation of caspase-9

death activators

TNF-α

lymphotoxin

FasL (Fas ligand)

reactive oxygen species

process

release of ATP and UTP (“find me” signal)

exposure of phosphatidylserine (“eat me” signal)

phagocytic release of antinflammatory cytokines IL-10 & TGR-β

p53

functions as tumor suppressor gene

expressed as the protein p53

inhibits action of Cdk2

genetically-engineered adenovirus ONYX-015

INK4a

functions as tumor suppressor gene

expressed as the protein p16^INK4a

inhibits action of Cdk4

ATM [ataxia telangiectasia mutated]

ATM detects DNA damage & maintains telomere length

MAD [mitotic arrest deficient]

proteins bind to kinetochore until spindle fiber attachment

mutations may lead to aneuploidy

HTLV-1 [human T cell leukemia virus-1]

Tax protein

kinesin involvement

G₀

cell leaves the cell cycle, temporarily or permanently

examples: neurons, lymphocytes

active repression of genes for mitosis

Mitosis ¹

distribution of complete genome to two daughter nuclei

duplication of chromosomes during S

dyads, each with two sister chromatids

cohesins

chromosome condensation

condensin

separation of sister chromatids

distribution of sister chromatids to daughter nuclei

stages of mitosis

prophase

centrosomes move to opposite ends of the cell

mitotic spindle forms

microtubules

tubulin

chromosomes become compact

prometaphase

nuclear envelope disintegrates

lamins

kinetochore appears at centromere

spindle fibers attach to kinetochores and chromosomal arms

kinetochores attached to opposite pole centrosomes

metaphase

dyads positioned at metaphase plate

anaphase

sister kinetochores separate and move toward their respective centrosomes

separase

securin chaperone

anaphase promoting complex destroys securin

cohesins broken down

telophase

nuclear envelope reforms

chromosomes disperse

cytokinesis

division of the cell

actin filament belt formed

interaction of actin of myosin

Meiosis ²

distribution of haploid genome to daughter nuclei

two consective divisions: meiosis I & meiosis II

no S phase between divisions

stages of meiosis

meiosis I

prophase I

more complicated than mitotic prophase

chromosomes appear already doubled

pairing of homologous dyads (each dyad consists of two sister chromatids) joined by cohesins

aligned along their lengths to form tetrads (bivalents)

chiasmata & crossing over

results in genetic recombination

synaptonemal complex

metaphase I

microtubules of spindle fibers attach sister kinetochores which are pulled to opposite poles

anaphase I

cohesins break down

chiasmata separate

homologous dyads moved to respective poles

results in random assortment of chromosomes

humans have 46 chromosomes, so 2²³, or 8388608, different combinations

telophase I

meiosis II

meiosis I is the reduction division

behavior of chromosomes in meiosis II is just like mitosis

at metaphase II, spindle fibers attach the kinetochores of the dyad to different poles

at anaphase II, chromatids separate (thus becoming chromosomes) and move to their respective poles

errors in meiosis

aneuploidy

caused by nondisjunction

monosomy (except X: Turner syndrome) lethal

Turner syndrome images

trisomy (except X, 13, 18, & 21) lethal

trisomy 13: Patau syndrome

images of trisomy 13

trisomy 18: Edwards syndrome

images of trisomy 18

trisomy 21: Down syndrome

images of trisomy 21

trisomy X: Triple-X syndrome

Triple-X syndrome images

Klinefelter syndrome (XXY or XXXY)

Klinefelter syndrome images

Jacob syndrome (XYY)

XYY syndrome karyotype

deletions

cri-du-chat syndrome

cri-du-chat syndrome images

Questions for thought

1.		What role does the centriole play in cell division?
2.		What does the abbreviation CDK stand for? What is a cyclin-CDK complex, and how does it work?
3.		What is a cell-cycle checkpoint? Describe how different checkpoints operate.
4.		Mutations in genes whose products are involved in DNA repair are often associated with an increased risk of cancer. What does this observation imply about the role of spontaneous mutations in the development of cancer?
5.		What is the genetic significance of the fact that gametes contain half the chromosome complement of somatic cells?
6.		What are some important differences between the first meiotic division and the second meiotic division?
7.		List the phases of mitosis and outline the events that occur in each.