M.B.Ch.B, MSC, DCH (UK), MRCPCH Molecular Biology Lec.1 Dr. Mohammed Hussein M.B.Ch.B, MSC, DCH (UK), MRCPCH

Molecular Biology

Main Topics Nucleic acid structure and organization DNA replication and repair Transcription and RNA processing The genetic code, mutation, and translation Genetic strategies in therapeutics Techniques of genetic analysis

Human Molecular Biology Human Molecular Biology is an introduction to health and disease for the new generation of life scientists and medical students. Good health is a matter of having the right molecules in the right place at the right time. This may seem self-evident, but the idea that health is determined mainly by molecules has only gained acceptance in recent years.

Nucleic acid structure and organization Lecture 1 Nucleic acid structure and organization

Objectives By the end of this lecture, one should able to Understand the concept of central dogma of molecular biology Recognize the structure of the nucleic acids Know the types of the nitrogenous bases present in the DNA and RNA Understand the process of base pairing Know how to use Chargaff's rule to calculate the amount of nitrogenous bases in DNA molecule Understand the packaging of the DNA in the nucleus Know the differences between heterochromatin and euchromatin

Central Dogma of Molecular Biology

Central Dogma of Molecular Biology An organism must be able to: Store its genetic information. Preserve these information. Pass that information along to future generations. Express that information as it carries out all the processes of life.

Central Dogma of Molecular Biology

DNA

The Four Scientists who discover the DNA

Nucleic Acid Structure and Organization

Nucleic acids

DNA = Deoxyribonucleic Acid Nucleic Acids RNA = Ribonucleic Acid DNA = Deoxyribonucleic Acid

Nucleic Acid Structure Nucleic acids are polymers of Nucleotides

Nucleotide

What is nucleotide?

Nucleotide consist of three components: Five-carbon sugar (pentose) Nitrogenous base Phosphate group 3 2 1

Five-Carbon Sugars (Pentose) Nucleic acids are classified according to the pentose they contain. If the pentose is: Ribose RNA (RiboNucleic Acid) Deoxyribose DNA (DeoxyriboNucleic Acid)

Numbers The numbers identifying the carbons of the sugar are labeled with “primes” Number 1 (1՜) Number 2 (2՜) Number 3 (3՜) Number 4 (4՜) Number 5 (5՜)

Nitrogenous Bases Adenine Guanine Cytosine Uracil Thymine Purines Is an organic molecule with a nitrogen atom that has the chemical properties of a base Adenine Guanine Cytosine Uracil Thymine Purines Pyrimidines

Nitrogenous Bases RNA has A, G, C, U DNA has A, G, C, T They are Pure As Gold They are CUTe and thin RNA has A, G, C, U DNA has A, G, C, T

Nitrogenous base is attached to the 1՜ carbon of the pentose sugar. 5 1 4 3 2

Nucleic Acids Are polymers of nucleotides joined by: 3՜, 5՜-phosphodiester bonds; that is a phosphate group links the 3՜ carbon of a sugar to the 5՜ carbon of the next sugar in the chain.

Base Sequence T Example: 5՜-TCGA-3՜ or TCGA C G A The base sequence of a nucleic acid strand is written in the: 5՜→3՜ direction (left to right). Example: 5՜-TCGA-3՜ or TCGA T C G A

DNA is double-stranded (dsDNA) RNA is single-stranded (ssRNA)

The double-stranded DNA (dsDNA) The two strands are antiparallel (opposite in direction) The two strands are complementary A always pairs with T G always pairs with C Thus, the base sequence on one strand defines the base sequence on the other strand. Purine with Pyrimidine

A = T G = C Adenine Guanine Thymine Cytosine Purine Pyrimidies

MNEMONIC A always pair with T (both letters are of straight lines) G always pair with C (both letters are of curved lines) A bind to T by 2 bonds ( A to T by 2) G bind to C by 3 bonds ( G to C by 3) C and T are single rings (cute are thin), while A and G are double rings

A to T by 2 G to C by 3 CUTE are thin Deoxyribose Sugar T C C G T A A Phosphate group

Erwin Chargaff

Erwin Chargaff Chargaff discovered two rules that helped lead to the discovery of the double helix structure of DNA. The first rule was that in DNA the number of guanine units is equal to the number of cytosine units, and the number of adenine units is equal to the number of thymine units. This hinted at the base pair makeup of DNA. The second rule was that the relative amounts of guanine, cytosine, adenine and thymine bases vary from one species to another. This hinted that DNA rather than protein could be the genetic material.

Chargaff’s Rule % A = % T and % G = % C Example a sample of DNA has 10% G; what is the % T?

% G = % C, as G= 10% so C= 10% %G + %C = 20% therefore, % A + % T must total 80% 40% A and 40% T Answer: 40% T

DNA Helix Most DNA occurs in nature as a right-handed double-helical molecule known as Watson-Crick DNA or B-DNA. There are about 10 base pairs per complete turn of the helix.

Organization of DNA Large DNA molecules (about 2 meters length) must be packaged in such a way that they can fit inside the nucleus (about 6 µm) and still be functional

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Nucleosome Nuclear DNA associated with histones and nonhistone proteins

Cells in interphase contain two types of chromatin: Euchromatin (more opened and available for gene expression) Heterochromatin (much more highly condensed and associated with areas of the chromosomes that are not expressed.)