Molecular Organisation of Centromere and Telomere

Chromosomes are the physical carriers of genetic material, and their functional integrity during the cell cycle depends critically on two specialized regions:

• the centromere, essential for chromosome movement and segregation, and
• the telomere, essential for chromosome stability and replication.

Although both appear as specific regions under the microscope, modern molecular biology has revealed that they are highly organized DNA–protein complexes with unique sequence motifs and epigenetic characteristics.

2. Centromere – Structure and Organisation

2.1 Definition

The centromere (primary constriction) is the chromosomal region where kinetochore proteins assemble, allowing attachment of spindle microtubules during mitosis and meiosis.
It ensures accurate distribution of chromosomes to daughter cells.

2.2 Position and Types

Based on the position of the centromere, chromosomes are classified as:

Type	Position	Shape during Anaphase
Metacentric	Middle	V-shaped
Submetacentric	Slightly off-center	L-shaped
Acrocentric	Near one end	J-shaped
Telocentric	At the end	i-shaped
Holocentric	Diffuse (along entire length)	Parallel movement (e.g., Caenorhabditis elegans)

2.3 Molecular Composition

The centromere is a complex DNA–protein domain containing:

A. DNA Components

1. Repetitive DNA Sequences:
   • Centromeric DNA consists mainly of satellite DNA – highly repetitive, non-coding sequences.
   • In humans: α-satellite DNA (171 bp repeats) forms the major component.
   • In plants: CentO (155 bp) repeats in rice, pAL1 in maize, and TrsA in Arabidopsis.
2. CEN DNA (Centromeric Core DNA):
   • A small region (120–150 bp in yeast) responsible for kinetochore binding.
   • Yeast has a “point centromere”, while higher eukaryotes have “regional centromeres” several megabases long.
3. Centromeric Heterochromatin:
   • Rich in AT base pairs, tightly packed, late-replicating.
   • Contains transposon-like elements and tandem repeats.

B. Protein Components

The centromeric chromatin differs from normal nucleosomes.
It contains specialized histone variants and kinetochore proteins:

Protein	Function
CENP-A (CENH3 in plants)	A centromere-specific variant of histone H3 that replaces canonical H3; imparts unique chromatin identity.
CENP-B, CENP-C, CENP-E	Structural proteins forming the kinetochore complex.
CENP-T, CENP-N	Link centromeric DNA to microtubules.
Topoisomerase II	Relieves torsional stress during condensation.
Cohesins	Hold sister chromatids together until anaphase.

2.4 Kinetochore Organisation

The kinetochore is a trilaminar proteinaceous structure formed on the centromere during cell division.

Layer	Composition and Function
Inner plate	Attached directly to centromeric DNA containing CENP-A chromatin.
Middle layer	Contains structural proteins (CENP-C, CENP-H) forming the core scaffold.
Outer plate	Binds to microtubules through motor proteins like dynein and kinesin.

Each kinetochore binds 20–40 microtubules in human cells, depending on the chromosome size.

2.5 Epigenetic Identity of the Centromere

Centromere identity is epigenetically inherited — not strictly determined by DNA sequence but by:

• Presence of CENP-A nucleosomes,
• Histone modifications (H3K9me3, H4K20me3), and
• DNA methylation patterns.

This ensures centromere function is maintained across generations, even if the sequence composition varies.

2.6 Function of Centromere

1. Attachment site for spindle fibres via kinetochores.
2. Ensures equal segregation of chromosomes during cell division.
3. Maintains sister chromatid cohesion until anaphase.
4. Involved in chromosome movement through motor proteins.
5. Prevents chromosome breakage during segregation.

3. Telomere – Structure and Organisation

3.1 Definition

A telomere is a specialized repetitive DNA–protein complex present at the ends of linear chromosomes, providing stability, replication completeness, and protection against degradation.

Telomeres were first described by Müller (1938) and McClintock (1941), who observed that chromosome ends possess unique structures preventing fusion.

3.2 Molecular Composition of Telomeres

A. DNA Components

1. Repetitive Sequences:
   • Consist of short tandem repeats rich in guanine (G-rich strand).
   • Common motif:
     • Humans and vertebrates: (TTAGGG)ₙ
     • Plants (Arabidopsis): (TTTAGGG)ₙ
     • Tetrahymena: (TTGGGG)ₙ
2. Single-Stranded Overhang:
   • The G-rich 3′ overhang (~100–200 nucleotides) folds back and invades the double-stranded region, forming a T-loop (telomeric loop) and a D-loop (displacement loop) structure for protection.

B. Protein Components

Telomeric DNA is coated by specific protein complexes forming the shelterin complex (in vertebrates) or telosome (in plants and yeast).

Protein	Role
TRF1, TRF2 (Telomeric Repeat-binding Factors)	Bind double-stranded telomeric DNA; maintain T-loop formation.
POT1 (Protection of Telomeres 1)	Binds to single-stranded G-rich overhang.
TIN2, TPP1, RAP1	Link TRF1/2 and POT1, stabilizing the telomere complex.
Telomerase enzyme	Adds telomeric repeats to the 3′ ends during replication.

3.3 Telomerase and Replication of Telomeres

Because DNA polymerase cannot fully replicate the 3′ ends of linear chromosomes (the “end-replication problem”), cells use telomerase, a ribonucleoprotein reverse transcriptase enzyme.

• Telomerase components:
  • TERT (Telomerase Reverse Transcriptase) — protein component.
  • TERC (Telomerase RNA Component) — RNA template (e.g., 3′-CAAUCCCAAUC-5′ in humans).

Function:
Telomerase extends the G-rich strand by adding repeats complementary to its RNA template, preventing telomere shortening during successive cell divisions.

3.4 Functions of Telomeres

1. Chromosome End Protection:
   • Prevents chromosome ends from being recognized as DNA breaks.
2. Prevention of End-to-End Fusions:
   • Shelterin complex inhibits DNA repair machinery from ligating ends.
3. Complete Replication:
   • Telomerase ensures full replication of chromosome ends.
4. Nuclear Architecture:
   • Anchors chromosomes to the nuclear periphery.
5. Aging and Disease:
   • Telomere shortening is associated with cellular aging (senescence), cancer, and genomic instability.

3.5 Comparison: Centromere vs. Telomere

Feature	Centromere	Telomere
Location	Primary constriction (middle region)	Terminal ends of chromosome
DNA Type	Satellite repetitive DNA	Tandem G-rich repeats
Proteins	CENP complex (CENP-A, CENP-B, etc.)	Shelterin complex (TRF1, TRF2, POT1, etc.)
Function	Kinetochore formation, chromosome segregation	End protection, replication completion
Replication Timing	Late S-phase	Late S-phase (with telomerase)
Chromatin Type	Constitutive heterochromatin	Specialized heterochromatin
Epigenetic Marker	CENP-A histone variant	G-quadruplex DNA, telomerase activity

3.6 Structural Overview Diagram (Conceptual)

Chromosome:

   [Telomere] — [Euchromatin] — [Centromere] — [Euchromatin] — [Telomere]

Telomere: (TTAGGG)n repeats → T-loop → Shelterin complex

Centromere: α-satellite repeats → CENP-A nucleosomes → Kinetochore attachment

4. Summary

Aspect	Centromere	Telomere
Primary role	Chromosome segregation	Chromosome end protection
DNA nature	AT-rich satellite repeats	GC-rich tandem repeats
Protein complexes	Kinetochore, CENPs	Shelterin, telomerase
Histone modification	H3 variant CENP-A	Histone H3K9me3, TERRA RNA
Dynamic function	Microtubule attachment	Replication and aging regulation

Both centromeres and telomeres are specialized chromosomal domains essential for genome integrity.

• The centromere ensures faithful segregation of chromosomes through kinetochore formation and spindle attachment.
• The telomere maintains chromosome stability, prevents end-to-end fusion, and regulates cellular lifespan through controlled telomerase activity.

Together, they represent the molecular guardians of chromosome architecture — safeguarding genetic continuity across generations.

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