GENETICS الفريق الطبي االكاديمي. Genomic DNA, Genes, Chromatin. DONE BY : Obadah Abubaker & Shady Soghayr. Page 0

Transcription

1 GENETICS ومن أحياها Genomic DNA, Genes, Chromatin الفريق الطبي االكاديمي Genomic DNA, Genes, Chromatin DONE BY : Obadah Abubaker & Shady Soghayr Page 0

2 Genomic DNA, Genes, Chromatin Dr. Nabil Bashir a). Genetic dogma Genomic DNA, Genes, Chromatin 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 1

3 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 2

4 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 3

5 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 4

6 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. عن نفس الل حك ناه فوق The same thing for the dgmp (dgdp or dgtp and (ممكن pyrimidines(dcmp,dcdp,dctp and the same thing for the rest). The only structure difference between ribonucleotide and deoxyribonucleotide in carbon number 2 of the sugar there is a Page 5

7 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 6

8 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 7

9 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, عن لما عط ك ستراند مثل الصورة ف األعلى نقرأها من 5 برا م الى 3 برا م بح ث كون الترت ب C, G, A, T وف حالة أعط ت هذا الترت ب عل ك أن تعلم أن C هو الذي حتو على ال group) 5 prime(has a free phosphate وهو اول ن كل وتا د وال T حتوي على ال group) 3prime (has a free hydroxyl وهو اخر ن كل وتا د. مالحظة هذه الفكرة مشروحة ف الدق قة 33:03 تقر با. Page 8

10 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 9

11 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 Page 10