Topic 3 - Molecular Basis of Inheritance

Who discovered the double helical model for DNA structure and when?

Watson and Crick in 1953

Adenine with

Thymine (double bond)

Cytosine with

Guanine (triple bond)

What does a DNA nucleotide consist of?

1. a nitrogenous base

2. a pentose sugar (deoxyribose)

3. a phosphate group

explain the 3’-5’ phosphodiester bond

the OH on the 3’ prime end of one carbon links itself to the phosphate group on the 5’ prime end of another carbon

Describe a bacterial chromosome

Double stranded circular DNA molecule

Describe a Eukaryotic chromosome

Double Stranded linear DNA molecule which is associated with a large amount of proteins called histones

Levels of chromatin packing in a eukaryotic chromosome

1. DNA

2. Nucleosomes

3. 30mn fiber

4. Looped domains

5. Metaphase chromosome

DNA double helix measurement

20A (2nm)

3 Nucleosomes

110A (11nm)

Chromatin fiber

300A (30nm)

Looped domains

3000A (300nm)

Section of Metaphase chromosome

7000A (700nm)

Entire Metaphase chromosome

1.4μm

Nucleosome Structure

Consists of 8 histone molecules, H2A, H2B, H3, H4 and double stranded DNA

What is the role of H1 histone?

Stabilizes the interaction between DNA and nucleosomal histones

Euchromatin

Loosely packed chromatin

Enables replication, transcription and gene expression

Heterochromatin

Highly Condensed chromatin

Inhibits replication, transcription and gene expression

Active and Inactive form of chromatin

Active : Euchromatin

Inactive : Heterochromatin

During interphase, do we have Euchromatin or Heterochromatin?

Euchromatin

During Mitosis, do we gave Euchromatin or Heterochromatin?

Heterochromatin

Histone Acetylation

Heterochromatin → Euchromatin

Histone Deacetylation

Euchromatin → Heterochromatin

What does DNA polymerase do?

It only adds NUCLEOTIDES int he 5’-3’ direction

What does DNA polymerase I do?

It degrades RNA primers and replaces them with DNA nucleotides

What does DNA polymerase III do?

It synthesizes Okazaki fragments by adding nucleotides to each primer in the 5’-3’ direction

What does Primase do?

It synthesizes short DNA primers by using the parental DNA as a template

The 3 prime end is the starting point

What dies DNA ligase do?

It joins the DNA fragments to the Okazaki fragments

Role of telomeres

They protect the chromosomal ends from erosion

Telomerase

Inactive in Somatic cells

Only activated by germ cells, stem cells, hair follicle, lymphocytes and several types of cancer cells

It also conserves the telomere length

Name the DNA repair mechanisms

1. MMR

2. BER

3. NER

MMR

Mismatch Repair

Corrects errors made during base pairing and replication errors

BER

Base Excision Repairs

Removes damaged bases

NER

Nucleotide excision repairs

Removes bulky DNA lesions

Xeroderma Pigmentosum

It is an AUATOSOMAL RECESSIVE disorder

In this case the NER repair mechanism is inactive

We have mutation in the genes

What do Replication errors cause? Which repair mechanism is activated?

They cause Mismatched Bases

MMR

What do chemicals cause? Which repair mechanism is activated?

They cause chemical modification of bases

BER

What do Pyrimidine and dimers cause? Which repair mechanism is activated? Which inherited DNA disorder is linked to this case?

They cause bulky DNA adducts

NER

Xeroderma Pigmentosum

What does Ionizing Radiation cause? Which inherited DNA disorder is linked to this case?

It causes double-strand breaks

BRCA1 and BRCA2 defects