CELL DIVISION

 Prenatal life- most cells divide and grow as baby grows

 Few cells lose ability like neurons as cells mature and differentiate
 Others persist throughout lifetime, e.g.: haematopoietic cells in bone marrow
 Many stem cells divide infrequently
 Daughter cells undergo multiply divisions until they die out
 Different rates in different tissues

CELL CYCLE
 Time between birth of a cell to its division to produce 2 daughter cells
 Minimum 12 hours
 4 phases
o G1
o G2 INTERPHASE
o S
o M

G1 PHASE
 cells respond to growth factors that initiate cell cycle
 Irreversible decision
 Most of the machinery needed to carry out division are produced
 Cells that no longer divide enter G0 phase or quiescent phase
 On stimulation they can be induced to divide again
 But tumor suppressor genes block them in G1
 Therefore, any lack of tsg can cause unchecked proliferation and development of cancer

S PHASE
 Dna synthesis takes place
 DNA content of cell doubles at end of this phae

G2 PHASE
 Prepares to divide
 Ends with onset of chromatin condensation and breakage of nuclear membrane

 6-8,2-4,1-2 hours duration (s, g2, m) respectively

 G1 variable 2-100 hours
 Progress of cycle driven by activity of CDK cyclin dependent protein kinases
 Kinases get activated by binding of cyclin subunit
 Each stage of cycle characterised by activity of 1 or more CDK- cyclin pairs
 Transitions between cell stages triggered by highly specific proteolysis of cyclins
 Target coated by e3 ubiquitin ligase which coat the unit with ubiquitin which is recognised by proteasome
 Cdk1 actovation initites g2 to m by a and b cyclins
 Exit frommitosis anaphase promotoig complex or cyclosome apc/c --- amrks
 P53 imporatnt negative regulation system without which malignancy occurs

MITOSIS AND MEIOSIS

 Results in distribution of identical copies of parent genome to 2 daughter somatic cells
 Meiosis-divisions immediately before final production of gametes halve the chromosome number of cell so
that at fertilisation diploid number is restored
 Also includes a phase of crossover of genetic material between homologous chromosomes for variety
MITOSIS
 S phase – new dna synthesised
 Dna doubled to 4N
 Chromosome 2X
 This number gets halved between 2 daughter cells
 Both cells are diploid
 4 phases
o Prophase
o Metaphase
o Anaphae
o Telophase

PROPHASE
 Chromatin shortens, thickens and become recognisable chromosmes
 Chromosome has duplicate chromatids which are products of dna replication
joined at centromere
 Centrioles separate outside nucleus and move to opposite poles
 Microtubules start assembling from them and others radiate to form asters
 By the end of this phase, nucleoli disappear and nuclear membrane disintegrates
to release chromosome

METAPHASE
 Microtubules attach to centromeres
 Chromosomes move to equatorial plane of spindle
 Late metaphase- cytoplasmic movement ensure distribution of
organelles across both sides

ANAPHASE
 Sister chromatids attached to opposite poles by microtubules attached to their
centromeres
 Proteolytic cleavage of cohesion which holds the replicated chromatids together
 Each move to opposite poles
 Both clusters are 2N

TELOPHASE
 Nuclear membranes reform
 Uncoiling of chromosomes and appearance of nucleoli
 Cytoplasmic division through formation of cleavage furrow
 Actin and myosin facilitate furrow formation by contracting
 Failure of disjunction leads to clustering and increase or decrease in
number of chromosomes according to which cell its in
MEIOSIS
PROPHASE I
 Long and comples
 5 stages
o Leptotene
o Zygotene
o Pachtene
o Diplotene
o Diakinesis

LEPTOTENE
 Homologous chromosomes-maternal and paternal copies of the same chromosome- find each other
 Genetic recombination initiated
 2 xes

ZYGOTENE
 Synapsis occurs by which the homologous chromosomes become intimately connected by synaptonemal
complex
 Begins at telomeres and often clusters to one side of nucleus
 Bouquet stage
 Synapsed homologues-bivalents
 Sex chromosomes also synapse at zygotene in a short dna sequence called pseusoautosomal region
 Chiasmata- knots that hold these chromosmes together

PACHYTENE
 Synapsis complete
 Bivalents appear as one
 Gene recomb over
 1 per chromosome arm usually
 Can go upto 5

DIPLOTENE
 Complex disassembles
 Pairs separate except at complex chiasmata
 Ovaries primary oocytes freeze at this stage until just before ovulation

DIAKINESIS
 Prometaphase of first meiosis

METAPHASE 1
 Same as mitosis except chromosomes are bivalent not single attached to spindle
 Arrange so that homologous pairs occupy middle
 Centromeres of both chromatids act as one sp that they disjoin from the opposrite
 Otherwise non-disjunction causes aneuploidy leading to foetal loss

ANAPHASE AND TELOPHASE 1

 Cleavage of cohesion
 Chiasmata break
 Migrate to opp poles
  But sister centromeres and chromatids don’t separate
 Just the homologous pair
 Eggs- division produces one egg and one polar body
 males- not fully complete div so are joined by small bridges of cytosol

MEIOSIS II
 After short interval with no dna synthesis
 Centromeres of sister chromatids remain close but rotate to face opposite poles
 So, they’re pulled apart
 Like in mitosis