CHROMOSOMES

S T RC T U R E A N D F O L D I N G
Cell Cycle Phases
S G2
G1
Initiation of M
Preparation of
Phase and Proteins
DNA Replication DNA Replication Formation

M
Division of cells
CHROMATIN-In Go and Interphase stage of DNA exist as nucleoprotein
complex.
CHROMOSOME- Chromatin, during M-phase is converted into a more
condensed form.
CHROMATID- one half of a replicated chromosome
Protein that fold DNA- HISTONE
Packaging of DNA Transcript that
encode-S-phase
specific
histones lack
poly-A tail
Histones Non-Histones

Replication Replication
Independent Dependent

H1 H2A H2B

Synthesized during S Phase H4 H3

HISTONES CONTENT
H1 LYSINE
H2A LYSINE
H2B LYSINE
H3 ARGININE
H4 ARGININE
Nucleosomes 1st Level
A basic structural unit. Histone octamer 2 copies of each H2A, H2B, H3, H4
H3-H4 Tetramer and H2A-H2B Dimer.----CORE HISTONES
These mainly contains basic amino acids which will neutralise the negative
charge of DNA.
DNA wrap 1.7 turn in left handed coil around the histones.
PROTAMINE-fish and sperms instead of histones
This gives beads on string structure.
Micrococcal Nuclease cleaves between DNA-MONONUCLEOSOME (200bp)
Further trimming reduce the length to 165bp and further 147bp
This Nuclease is non-specific endo-exonuclease and it’s substrate are RNA and
DNA.
Linker DNA (50-60bp) separates each nucleosomes.
H1 is termed as Linker DNA
H1+ Nucleosomes= Chromatosomes
H3 AND H4 are first deposited followed by H2A and H2B.
Chaperones are crucial for the assembly
•Nucleoplasmin
•ASF1
•NAP1
•CAF1
30nm Fiber 2nd Level
Nucleosomes into fiber
SOLENOID MODEL- Nucleosomes follow each other along the same helical path
and occur sequentially
ZIGZAG MODEL- two strands containing stacked nucleosomes are wound into a
left handed manner.
Metaphase Chromosomes 3rd LEVEL
Loops of 30nm chromatin fiber, containing20-100kb of DNA are attached to a
central Scaffold. This includes non-histones acidic proteins.
Topoisomerase II,condensins etc. are bind to AT rich sequences.
Topoisomerase II has the ability of cutting and sealing both strands of DNA.
Condensin
Condenses chromosomes
Proteins are made up of Structural Maintenance of Chromosomes(SMC).
They are Chromosomal ATPase.
STRUCTURE-

N HINGE
C

Walker A domain Walker B domain

Cohesins have linking role in sister chromatids after replication.
HISTONE MODIFICATIONS

Acetylation Methylation Phosphorylation

Acetylation
Acetyl group are added to the N-terminus histone tail.
Amino Acid-Lysine
Enzyme-Histone Acetyl Transferases/Histone Acetylase

• Reduces affinity of histones for DNA. Results in formation of

30nm fiber.
• Acetylation is reversible by Deacetylase
Methylation
Amino Acids-Lysine and Arginine at N-terminus of Histone tails.
ENZYME- Methyl Transferase.
H3K9-gene silencing and condensation
H3K4- Transcription activation.
Domain-Chromodomain
Phosphorylation
Phosphorylation of H3 and H1
Focus on Metaphase Chromosome
Heterochromatin
Parts of chromatin that remain highly condensed.
Dark stain.
Transcriptionally inactive/silent.
Condensed state during interphase.
Marked with deacetylation and methylation at H3K9
 Constitutive
Heterochromatin
• Permanently condensed and
transcriptionally inactive
• Do not contain genes Falcultative
• Replicate late in S-phase
Heterochromatin
• Regions of euchromatin that can
convert into hetrochromatin
• Can be condensed and decondensed.
Euchromatin
Less coiled
Transcriptionally active
Acetylation and methylation H3K4 and H3K79.