Chromosome Structure and Mitosis

DNA – Genes – Genomes -Chromosomes

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Base pair (A-T)
 ILO
• Eukaryotic Chromosome Organization and basic
Structure
• Levels Chromatin condensation

• Roles of non-histone proteins - Mitotic chromosome

• Phases of the cell cycle

• Cell division – Mitosis

Eukaryotic Chromosome Organization
• The human genome is packaged into larger units known as chromosomes
—physically separate molecules that range in length from about 50 to 250
million base pairs.
• Each chromosome contains many genes and specific DNA sequences
required for chromosome replication and segregation
– Origins of replication (multiple)
– Centromeres (1)
– Telomeres (2)
• The chromosomes are established by the compaction of linear DNA with
specialized proteins, generating a series of coils and loops
• The complex of DNA and protein is called as chromatin
• Proteins bound to DNA are subjected to change during cell cycle
• In addition, chromosomes are associated with proteins required for gene
expression, DNA replication and repair
Basic Structure of a Eukaryotic Chromosome
Telomere
Genes
Coding DNA sequences that
Origin of replication encode specific proteins.
located between the
Origin of replication
centromere & telomeres
Kinetochore proteins
Centromere

Origin of replication
Non-coding sequences
-Repetitive DNA sequences
Origin of replication
interspersed throughout the
Genes
Repetitive sequences chromosome
Telomere -Telomeres
-Centromere
 Levels of eukaryotic chromosomal
organization
• Each chromosome consists of a long double stranded
DNA molecule
• These strands require further packaging to fit into
the cell nucleus
• The DNA duplex is tightly bound to
and wound around proteins
called histones
• The DNA-wrapped histones
are called nucleosomes
 Nucleosomes
• Basic structural unit of chromatin

• Every ~146 bp of DNA is coiled around a

core of 8 histone proteins

• Histone proteins consist a high proportion

of positively charged amino acids i.e
Arginine and lysine
•
• The positive charge facilitates to form ionic
bonds with negatively charged DNA
(phosphate backbone of DNA)

• Nucleosomes are connected by short DNA

sequences – ‘linker DNA’
 Main Classes of Histone proteins

• Four Core histones

- Two of each of H2A, H2B, H3 & H4

• Linker histone – H1

H1

H1
 DNA double helix

‘Beads on a string’
form

30 nm fibre (solenoid) of
packed nucleosome

The stages of
chromatin Radial loop domains
condensation (euchromatin
compaction level)

Further compaction of radial

loops around preexisting
scaffold proteins

Entire mitotic
chromosome
• The nucleosomes are further coiled into a solenoid
• This solenoid then organized into looped domains
• The final organization of the chromosome is
unknown but it appears to involve further radial
looping into rosettes around a preexisting scaffold of
proteins
Role of non- histone proteins in chromatin
condensation
• Cohesin
• Condesin
Cohesin
Cohesin

• Is a protein complex that regulates the separation of

sister chromatids during cell division.
• Keep the sister chromatids connected with each other
from the end of S phase to G2 phase and the
beginning of prophase of mitosis.
• In the middle of the prophase, cohesion along the
arms are released to free the arms of the sister
chromatids.
• Cohesins at the centromere is finally degraded at the
anaphase allowing each sister chromatids segregates
to opposite poles.
During Condensin
interphase,
condensin is in
the cytoplasm

Condensin
binds to
chromosomes
and compacts
the radial loops

Condensin
travels into
the nucleus
Condensins
• They are large protein complexes that play a central
role in chromosome assembly and segregation during
cell cycle

• During interphase, condensin is found in the

cytoplasm and they travel into the nucleus during M-
phase to bind to the chromosomes and further
compact the radial loops
 Heterochromatin vs Euchromatin
• Heterochromatin is the tightly packed
form of DNA, mainly consists of
genetically inactive genes with very
limited transcription

• In contrast, euchromatin is loosely

wrapped around the histone core as
they are rich in gene concentration
and often under active transcription
 Heterochromatin
Heterochromatin maintains the integrity of
chromosomes
• Constitutive – found Constitutive Facultative
around the centromere heterochromatin heterochromatin
and telomeres; poorly
expressed

• Facultative – can
interconvert upon
requirement
Classification of chromosomes
 Karyotype
• It is the arrangement of a complete set of
chromosome from a cell arrested at the
metaphase of the cell cycle
 Groups of
chromosomes
Interphase
G1-> S->G2
Cell Division I – Mitosis
 Mitosis
• Is the process in cell division by which the nucleus
divides

• Two stages
– Nuclear division
• Prophase
• Metaphase
• Anaphase
• Telophase
– Cytoplasmic division (Cytokinesis)

• Normally resulting in two new nuclei each of which

contains a complete copy of the parental
chromosomes
 Interphase
Two centrosomes,
each with centriole pairs
• Cell growth and
preparation for division
• DNA synthesis
Nuclear • Cells spend most of
membrane
their lives in interphase
• Longest part of the cell
cycle. (Some cells never
leave interphase)

Chromosomes as chromatin threads

 Prophase
Microtubules
forming mitotic spindle
• Chromatin condenses to
form chromosomes;
• Centrosomes migrate to
the poles;
• Nuclear membrane
breaks down
• Spindle forms and
kinetochore MTs attach
Sister chromatids to the mitotic
Centromere chromosomes
 Prometaphase Metaphase

Kinetochore
Nuclear membrane microtubules
fragmenting

Mitotic
spindle
Metaphase
plate
Polar microtubule

Astral
Kinetochore proteins attached microtubules
to centromere
Anaphase

Chromosomes • Sister chromatids

separate and now
daughter chromosomes
migrate to the poles
Telophase
• Spindle disappears
• The chromosomes
assemble in sets at the two
poles and begin to uncoil
• Nuclear envelope reforms
around each chromosome
set
• Nucleolus reappears
• Nuclear division by mitosis
is complete at this point
 Cytokinesis
• The division of the
cytoplasm that results
in two daughter cells
• Occurs at the end of
telophase.

**In plant cells, cytokinesis begins when a new cell wall forms
between the two new cells.

**In animal cells, the two new cells pinch and pull apart
(cleavage furrow is formed)
 Contractile ring of
microfilaments (Actin)

Animal Cell
 Plant Cell

Golgi derived vesicles

 Importance of mitosis
• Asexual reproduction – (offspring are "clones"
of their parent)
– Binary fission
– Budding
– Vegetative propagation

• Tissue regeneration
• Maintenance of genetic stability of a species

• Important for growth, repair and development

 Individual task
• Leave your notes aside, take a piece of paper
and draw the fully labelled spindle apparatus
formed during metaphase in mitosis and list
the function of each type of microtubule