genomic dna, genes, chromatin · اهايحأ نمو genomic dna, genes, chromatin page 1 genomic...

Genomic DNA, Genes, Chromatin ومن أحياها

Page 0

GENETICS

الفريق الطبي

االكاديمي

Genomic DNA, Genes, Chromatin

DONE BY :

Obadah Abubaker &

Shady Soghayr

GENETICS


Page 1


Dr. Nabil Bashir


a). Genetic dogma

b). forces that affect DNA double helical stability

c). Complexity of chromosomal DNA

i). DNA denaturation

ii). Repetitive DNA and Alu sequences

iii). Genome size and complexity of genomic DNA

d). Gene structure

i). Introns and exons

ii). Properties of the human genome

iii). Mutations caused by Alu sequences

e). Chromosome structure - packaging of genomic DNA

i). Nucleosomes

ii). Histones

iii). Nucleofilament structure


Page 2

Learning Objectives • Know what is meant by Genetic dogma • Understand the nature of the forces contributing to the

stability of the DNA double helix • Understand the process of DNA denaturation and the

relationship between melting temperature and the base composition of DNA

• know what repetitive sequences are and how they are arranged in the human genome

• Understand the mechanism by which Alu sequences have affected the LDL receptor gene

• recognize basic gene structure. • Know the basic characteristics of human nuclear and

mitochondrial DNA • Understand basic chromosome structure and how

DNA is packaged into chromosomes

Genetic dogma : THE FLOW OF GENETIC

INFORMATION

1. REPLICATION (DNA SYNTHESIS) 2. TRANSCRIPTION (RNA SYNTHESIS) 3. TRANSLATION (PROTEIN SYNTHESIS)

• DNA replication :transferring genetic information

from a DNA molecule to form a new DNA molecule (

will be identical to the precursor).

• Transcription : transfer genetic information from DNA

to RNA(RNA is synthesized from a single strand

DNA (template DNA )).


Page 3

• Translation (protein synthesis) : transfer of genetic

information from RNA to protein

• Reverse transcription : transfer genetic information

from RNA to DNA (happens in many viruses)

DNA needs enzyme activity to replicate.

• Genetic diseases occur because of mutations in DNA.

Many of these mutations affect the repair of other

mutations that occur during DNA replication or at other

times, which in turn affect the flow of genetic information

from DNA to RNA (transcription and processing) and

from RNA to protein synthesis (translation). Many of these

mutations also affect the structures of the resulting

proteins, affecting their functions.

• Mutation :change in the sequence

• Mutation is the base to all genetic diseases

5-Methylcytosine (5mC).

A common base modification in DNA results from the

methylation of cytosine, giving rise to 5-methylcytosine (5mC).

5mC is highly mutagenic.

(5mC) residues are often clustered near the promoters of genes

in so-called "CpG islands.“

when this mutation is in the promoter region it is called

CG(island) hotspot

The problem that arises from these methylations is that

subsequent deamination of a 5mC results in the production of

thymine, which is not foreign to DNA. As such, 5'-mCG-3' sites

(or mCpG sites) are "hot-spots" for mutation, and when mutated

are a common cause of cancer.


Page 4

structure of the nucleic acid :

1.Nitrogenous base ( purines and pyrimidines)

Purines have 2 rings while pyrimidines have 1 ring

Ex. Of purines : Adenine and Guanine

Ex. Of pyrimidines : Thymine ,Cytosine and Uresile

2.Sugar (pentose)

In the case of DNA :at carbon (2) there is no oxygen (just hydrogen)

There is a phosphodiester bond between the carbon (5) (hydroxyl group) and the phosphate ( can be α,β or Ɣ )

3.Phosphate

Can be divided to :

Poly deoxy nucleotide (eg.DNA)

Poly nucleutide (eg.RNA)

Pentose sugar is attached to the nitrogenous base by a N-glycosidic bond (covalent bond between a nitrogen of a nitrogenous base and the sugar).


Page 5

On carbon number 5 of the sugar there is a phosphodiester bond

between the hydroxyl group of the sugar on carbon number 5 and a

phosphate (alpha phosphate or beta phosphate or gama phosphate)

There are three phosphate group attached in a phosphoester bond

with the oxygen of the deoxyribose in the deoxynucleutides.

The left structure in the figure is called deoxynucleotide triphosphate

, if one phosphate is removed then the name is

deoxynucleotidediphosphate , if only one phosphate is found then

the name is called deoxynucleotidemonophosphate , if the base is

adenine then the structure that has adenine, sugar and phosphate is

abbreviated as dAMP(d: deoxy , A: adenosine (not adenine) , M:

mono , P: phosphate) if 2 phosphates are there : dADP , if 3

phosphates : dATP.

The same thing for the dGMP (dGDP or dGTP ً حكٌناه فوق ٌعنً نفس الل

and pyrimidines(dCMP ,dCDP,dCTP and the same thing for the(ممكن

rest).

The only structure difference between ribonucleotide and

deoxyribonucleotide in carbon number 2 of the sugar there is a


Page 6

hydroxyl group in ribonucleotide.

(oxynucleotide)((ribonucleotidefound in RNA)) and there is a

hydrogen group in deoxyribonucleotide((deoxyribonucleotide

found in DNA))

deoxyribonucleotide in DNA gives stability to the DNA

ribonucleotides found in RNA they cause instability

So, it is very important to have deoxy sugars in our DNA for the sake

of stability of our genes, if we have ribonucleotides our genes will be

unstable ,and they will always be destroyed .

**Not necessary to memorize the structure but you must remember

the features of each of the nitrogen bases at least differentiate

between purines and pyrimidines and if you are good ,also

differentiate between adenine and guanine as well as between

different pyrimidines (which one has amino group , which one has

oxyketo group , which one has methel group, remember these

general features.)

One strand of DNA


Page 7

when these nucleotides (deoxyribonucleotides or polyribnucleotides) are

linked to each other they will form polydeoxyribonucleotides (means

DNA) or polyribnucleotides (means RNA)

From the 3 prime carbon of first sugar there is a phosphoester bond

with the alpha phosphate (the first phosphate) of the second

nucleotide

So, between 3 prime of the first sugar with the 5 prime of the second

deoxy sugar you have a phosphodiester bond and this is repeated

between 3 prime of the second with the 5 prime of the third and it

goes to the end .

The polynucleotide that is form has 2 ends : one end is called 5 prime

end and the other end is called 3 prime end .

Why we named it as 5 prime end ?

Because there is a phosphate which is 3 on the 5 prime of the first

nucleotide so this is the beginning of the DNA molecule.

Why we named it as 3 prime end ?


Page 8

Because there is 3 hydroxyl group at the last nucleotide in the nucleic

acid .

So each nucleic acid has 2 ends ,the first on the beginning of any of

nucleic acid is called 5 prime end , and last nucleotide of any nucleic

acid is called 3 prime end.

What are the feature of 3 prime end and 5 prime end ?

5 prime ends have free phosphate groups while 3 prime end of any

nucleic acid has free hydroxyl group at the 3 prime end.

So nucleic acid (when we talk about one strand) it runs from 5 prime

to 3 prime ,you read it from 5 prime to 3 prime,

براٌم بحٌث 3براٌم الى 5ٌعنً لما ٌعطٌك ستراند مثل الصورة فً األعلى نقرأها من

هو الذي Cوفً حالة أعطٌت هذا الترتٌب علٌك أن تعلم أن C , G , A , Tٌكون الترتٌب

Tوهو اول نٌكلٌوتاٌد وال prime(has a free phosphate group) 5ٌحتوٌعلى ال

وهو اخر نٌكلٌوتاٌد . 3prime (has a free hydroxyl group) ٌحتوي على ال

تقرٌبا. 33:03مالحظة هذه الفكرة مشروحة فً الدقٌقة


Page 9

Genes are composed of sequence of deoxynucleotides they are

arranged in specific positions if any position has been changed that

means we have mutation .

DNA is found in a double strand )there are two deoxy

polynucleotides attached to each other ( while RNA is found in a

single strand but sometime you will see that single stranded of RNA

forming some double stranded regions within the RNA molecule for

specific reasons we will talk about it later.

Double stranded which is composed of two strands which are

complementary to each other and they run antiparallel and they

run in a helical structure or twisted .

This structure (helical) was discover in 1953 by Watson and Crick and

they published a paper and saying that DNA is composed of double

stranded molecules and they are in a helical structure .

Antiparallel: one strand runs from 5 prime to 3 prime and the

second strand runs in opposite (from 3 prime to 5 prime)


Page 10

Complementary:means that always thymine base pair with

adenine , cytosine base pair with guanine .

That means guanine can not base pair with adenine or thymine

because there are spaces that units this type of base pairs. (like

the prenciple of the ligand and the receptor) #specificity

The outside of the structure (the backbone )is rich in

phosphates and sugars and from the inside (inside the helical

structure) there are nitrogen bases.

The backbone is stabilized by covalent bonds (phosphodiester

bonds) while the inside base pairing is stabilized mainly by

hydrogen bonds and you will see 2 hydrogen bonds always

between adenine and thymine and 3 hydrogen bonds

between guanine and cytosine.

If any information was written badly (hard to study) or

was not clear

Please contact us

genomic dna, genes, chromatin · اهايحأ نمو genomic dna, genes, chromatin page 1 genomic...

Documents