Genetics Lecture Notes (Level 1, Semester 1) PDF

Genetics Nucleic Acid (DNA & RNA) LECTURE (1) DR. El-Sawy 0  Genetics Nucleic Acid (DNA & RNA) De...

Genetics Nucleic Acid (DNA & RNA) LECTURE (1) DR. El-Sawy 0  Genetics Nucleic Acid (DNA & RNA) Definition:  Long chains of repeated subunits (Nucleotides).  Building block of DNA & RNA  Present in body as: Def A. Poly-nucleotide (DNA - RNA ) OR B. Free nucleotides. A. Nitrogenous base : ‫قاعدة نيتروجينيه‬  Adenine.  Xanthine. Purines  Guanine.  Hypoxanthine. Structure Pyrimidine  Cytosine.  Uracil.  Thymine. B. Pentose sugar : ‫سكر خماسي‬ D-ribose.  in RNA 2-deoxy-D-  in DNA ribose. C. Phosphate (phosphoric acid). ‫فوسفات‬ NOTE Nucleoside  Nitrogenous base + Pentose sugar. Minor nitrogenous base  xanthine, hypoxanthine, uric acid & caffeine. DR. El-Sawy 1  Genetics Nucleic Acid (DNA & RNA) ‫ → قاعدة وسكر‬N glycosidic bond ‫ → فوسفات وسكر‬Phosphoester bond ‫ → قاعدة وقاعدة‬Hydrogen bonds Types : Base Nucleoside Nucleotide  Adenosine  AMP , ADP,ATP , Adenine  Deoxy adenosine  d. AMP, d. ADP , d. ATP  Guanosine  GMP , GDP, GTP , Guanine  Deoxy guanosine  d. GMP, d. GDP , d. GTP Xanthine  Xanthosine  XMP Hypoxanthine  Inosine  IMP  Cytidine  CMP , CDP, CTP , Cytosine  Deoxy cytidine  d. CMP, d. CDP , d. CTP Uracil  Uridine RNA ‫بس‬  UMP, UDP, UTP Thymine  Deoxy thymidine DNA ‫بس‬  d. TMP, d. TDP , d. TTP DR. El-Sawy 2  Genetics Nucleic Acid (DNA & RNA) Functions : ‫بناء و طاقة & مساعد ومنشط ومتبرع &استخدام ودوائي‬ Building blocks  of RNA and DNA Source of energy  ATP, GTP act as source of energy. Co-enzymes  NAD, FAD, Co-enzyme A. Mediate hormonal  c.AMP & c.GMP are 2nd messenger. action Activation of chemical  UDP- glucose → synthesis of glycogen. compounds  PAPS is a sulfate donor → synthesis of sulfolipids Chemical group donors  SAM is a methyl donor → transmethylation reactions.  Nucleotides analogues prepared by altering the base ring or sugar part. Synthetic Analogue  5-flurouracil (pyrimidine analogue): ↓ thymine Anti- cancer → ↓ DNA synthesis →↓ growth of cancer cells. Anti-  Allopurinol (hypoxanthine analogue). gout DR. El-Sawy 3  Genetics Nucleic Acid (DNA & RNA) Def :  Long chain of repeating subunits, called nucleotides  Responsible for storage of genetic information. Primary structure :  DNA is 2 strands of polynucleotides ( d.AMP , d.GMP , d.TMP , d.CMP). Structure  The nucleotides are linked by 3`,5` phosphodiester bond between :  3`hydroxyl group of one nucleotide  5`phosphate group of next nucleotide. 1. Alternating sugar-phosphate units  asymmetrical backbone of each strand. 2. Nitrogenous bases  projecting to the inside of 2 stands at right angle 3. Sequence of bases  determines the coding structure of DNA (genetic Characters information) 4. DNA sequences  written in 5` to 3` by latter abbreviation of bases (ex:- GCA). 5. Polarity: each strand has 2 ends :  One end (5`end) has free phosphate group.  Other end (3`end) has free hydroxyl group. DR. El-Sawy 4  Genetics Nucleic Acid (DNA & RNA) secondary structure (B-form of DNA) :  Waston and crick proposed structure of DNA in form of double helix (B- form) which is the common physiological form. 1. Right handed helix (its diameter =2 nm). 2. The 2 strands are anti-parallel: they run in opposite direction (one runs in the 5` to 3` direction while the other strand runs in the 3` to 5` Characters direction ) 3. Complementary base pairing: through hydrogen bonds Adenine pairs with Thymine through 2 hydrogen bond (A=T) Guanine pairs with Cytosine through 3 hydrogen bonds (GΞC) Melting temperature (Tm) Def : Temperature at which 50 % of helical structure is lost. Factors affecting :  Tm decrease if DNA contains higher proportion of AT base Types of bases pairs. p.H of medium  Tm Decreases if the medium is more alkaline.  Tm decreases if salt concentration is decrease. Salt concentration  salts is stabilizing agent. DR. El-Sawy 5  Genetics Nucleic Acid (DNA & RNA)  All RNA molecules are formed in the nucleus form DNA by RNA Formation polymerase (transcription), then most of RNA is transported to cytoplasm  Single strand. Structure  Contain 4 types of nucleotides (AMP, GMP, CMP, UMP) which are inter connected by phosphodiester bonds. Ribosomal RNA Transfer RNA Messenger RNA Small nuclear RNA Types (r.RNA) (t.RNA) (mRNA) (snRNA) 80% 15% 5% Less than 1% NOTE Small nuclear RNA : has 30 different species. DR. El-Sawy 6  Genetics Nucleic Acid (DNA & RNA)  80 % of total RNA  It is Brocken into few pieces associated with several proteins to form ribosome.  Mammalian ribosome Consist of 2 subunits: 1. Large subunit ( 60 S): Composed of 50 polypeptide chains & 3 types of rRNA (5S , 5.8S, 28S) 2. Small subunit ( 40 S): Composed of 30 polypeptide chains and 18S r.RNA The 2 together from 80 S ribosome DR. El-Sawy 7  Genetics Nucleic Acid (DNA & RNA)  15 % of total RNA.  Clover-leaf appearance.  Stabilized by hydrogen bonds between complementary bases (A=U) , (GΞC).  It has four arms: D arm  it ends in loop that contains dihydrouracil  It ends in loop contains sequence thymine , pseudouridine TΨC arm and cytosine Anti-codon  It ends in loop that contains 7 bases , three of 7 bases in arm middle of loop constitute the anti-codon.  It doesn’t end in loop. Acceptor arm  It ends in sequence CCA (5’ →3’), the 3’ end is site of attachment for amino acid that is carried by t.RNA. DR. El-Sawy 8  Genetics Nucleic Acid (DNA & RNA)  5% of total RNA.  Carries message from DNA to ribosome where it directs protein synthesis.  Each protein has specific m.RNA  Divided to three regions : 5’ untranslated  Not translated. leading sequence  Ends by cap.  Carries code for synthesis of specific protein. Translated coding  Each 3bases (codon) will be translated for specific sequence amino acid. 3’ untranslated  Not translated. tailing sequence:  Ends in poly (A) tail. DR. El-Sawy 9  Genetics Nucleic Acid (DNA & RNA) Compare between DNA & RNA : DNA RNA Occurrence Nucleus, Mitochondria Cytoplasm Storage & transfer of genetic Protein synthesis Functions information Bases A,G,C,T A,G,C,U Sugar Deoxy-ribose Ribose Strands 2 strands forms double helix One strand only One type 4 Types Types mRNA, tRNA, rRNA, snRNA Shape Double helix Variable Compare between different types of RNA : m.RNA t.RNA r.RNA More than 105 50-60 different Types 28S ,18S, 5S, 5.8S different species species Abundance 5% 15 % 80 % Unstable to very Stability Very stable Very stable stable Carries message Carries amino Constitutes from DNA to Functions acids for protein ribosome , site of ribosome to direct synthesis protein synthesis protein synthesis RNA polymerase I Type of polymerase (18S,5.8S.28S) RNA polymerase II RNA polymerase III responsible for RNA polymerase III synthesis (5S) DR. El-Sawy 10  Genetics Nucleic Acid (DNA & RNA) Fatima is a 44 year old lady, presented with severe pain in her right big toe, with inflammation of the joints. She was diagnosed as acute gouty arthritis. She had been taking allopurinol. Q : Explain chemical nature of allopurinol ?  Hypoxanthine analogue. Q : Explain mechanism of action of allopurinol ?  Inhibit xanthine oxidase →↓ production of uric acid. DR. El-Sawy 11