Molecules, Genes, and Disease

• Study notes on molecules, genes, and disease
• Covering DNA structure and chromosome organization

Central Dogma of Molecular Biology

• The Central Dogma is the flow of genetic information from DNA to RNA to protein in all organisms.
• In most organisms, DNA stores genetic information; some viruses use RNA.
• Central Dogma: DNA → RNA → Protein.
• In retroviruses like HIV, the information flow is: RNA → DNA → RNA → Protein, involving reverse transcription.

Nucleic Acids: DNA and RNA

• Nucleic acids are linear polymers of polynucleotides necessary for the storage and expression of genetic information.
• Two chemically distinct types of nucleic acids exist
• Deoxyribonucleic acid (DNA) is a polymer of deoxyribonucleotides, linked by 3'→5' phosphodiester bonds, carrying genetic information in all cellular life forms and some viruses.
• Ribonucleic acid (RNA) is a polymer of ribonucleotides linked by 5'→3' phosphodiester bonds.
• RNA functions as an intermediary in transferring genetic information from DNA to protein.

Nucleotides: Building Blocks of Nucleic Acids

• Nucleotides are the basic building blocks of DNA and RNA.
• Each nucleotide consists of three components: a nitrogenous base, a pentose sugar, and a phosphate molecule.
• Nucleosides are composed of a nitrogenous base and a pentose sugar only.nitrogenous base

Nucleotides Components

• Nitrogenous Bases: There are two types: purines and pyrimidines.
• Purines: Have a two-ring structure; includes adenine (A) and guanine (G).
• Pyrimidines: Have a one-ring structure; includes thymine (T), cytosine (C), and uracil (U).
• DNA contains A, G, T, and C, while RNA contains A, G, U, and C.
• Pentose Sugar: There are two types: ribose (in RNA) and deoxyribose (in DNA).
• Phosphate Group: Phosphate groups are strongly acidic and are a reason for calling DNA and RNA acids.

Nucleotides Structure

• Nucleotides are formed by the covalent bonding of phosphate, base, and sugar.

Nucleotides Nomenclature

• Adenine (A) in RNA becomes adenosine nucleoside and adenosine monophosphate (AMP) nucleotide
• Guanine (G) in RNA becomes guanosine nucleoside and guanosine monophosphate (GMP) nucleotide
• Uracil (U) in RNA becomes uridine nucleoside and uridine monophosphate (UMP) nucleotide
• Cytosine (C) in RNA becomes cytidine nucleoside and cytidine monophosphate (CMP) nucleotide
• Adenine (A) in DNA becomes deoxyadenosine nucleoside and deoxyadenosine monophosphate (dAMP) nucleotide
• Guanine (G) in DNA becomes deoxyguanosine nucleoside and deoxyguanosine monophosphate (dGMP) nucleotide
• Thymine (T) in DNA becomes deoxythymidine nucleoside and deoxythymidine monophosphate (dTMP) nucleotide
• Cytosine (C) in DNA becomes deoxycytidine nucleoside and deoxycytidine monophosphate (dCMP) nucleotide

Polynucleotides Chain: Formation and Characteristics

• Nucleotides are covalently linked via 3'→5' phosphodiester bonds to form polynucleotide chains.
• The resulting chain has polarity.
• Conventionally, bases are written in the 5' to 3' direction.
• DNA has two polynucleotide chains, while RNA has only one.
• Each single-strand nucleic acid chain has a polarity

Key Features of Double Helix DNA

• Double helix DNA follows the Watson-Crick Model (1953).
• DNA typically exists as a double-stranded helix molecule.
• Anti-Parallel: DNA is composed of two polynucleotide chains running in opposite directions, with one chain running in the 5'→3' direction and the other in the 3'→5' direction.
• Chargaff Rule: -A=T, G = C -Total purines=Total pyrimidines Complementary base pairing occurs; A pairs with T via two hydrogen bonds, and C pairs with G via three hydrogen bonds.

Double helix DNA: Watson-Crick Model (1953)

• Involves complementary base pairing and hydrogen bond formation.
• The sugar-phosphate backbone is on the outside, while the bases are on the inside.

Double helix DNA: Watson-Crick Model (1953)

• Secondary Structure: The two chains are twisted (coiled) around each other in a right-handed manner to form a double helix (B-Form).
• One complete turn contains 10 base pairs, with a spacing of 0.34 nm between base pairs.
• Two grooves, major (wide) and minor (narrow), are created.
• The bases in these grooves are exposed, allowing interaction with proteins or other molecules.

Double helix DNA: Watson-Crick Model (1953)

• Negative Charge: The third-OH group on the phosphate is free and dissociates a hydrogen ion at physiologic pH.
• Results in DNA helix having negative charges coating its surface, which facilitates the binding of specific proteins (histones and non-histones).

Key Features of Double Helix DNA

• DNA Denaturation & Renaturation: Double strands can separate into single strands by disrupting the hydrogen bonds using acidic or alkaline pH or heating
• (phosphodiester bonds are not by such treatment). Complementary DNA strands can reform the double helix under appropriate conditions.
• DNA Degradation: Phosphodiester bonds (in DNA & RNA) can be cleaved hydrolytically by chemicals or hydrolyzed enzymatically by nucleases
• There are three major structural forms of DNA: A, B, and Z

Ribonucleic Acid (RNA)

• RNA is a polymer of ribonucleotides covalently linked by 3'→5' phosphodiester bonds.
• It's single-stranded and has polarity, with bases written from 5'→3'.
• Phosphodiester bonds can be cleaved hydrolytically by chemicals or enzymatically by nucleases.

DNA Condensation

• A cell's genetic information, in the form of DNA,limited and has to contain billions of nucleotides that compose the cell's DNA.
• DNA has to be highly organized or condensed
• The DNA coils around proteins called histones, forming a beads-on-a-string-like structure called a nucleosome.
• The first level of DNA Package
• DNA wraps at several levels, compacted into a chromosome
• Specifically, a nucleosome is the fundamental unit of DNA packaging, composed of eight histone proteins (a pair of each of four types) that anchors nucleosomes to short "linker" regions
• This tightens the nucleosomes into fibers 30 nanometers (nm) in diameter which condenses to chromosome.
• Chromatin Fibers
• A compact of nucleic acids and proteins Chromosomes of most living cells
• Chromosomes: observable during M-phase or nuclear division for cell division

DNA Replication

• DNA synthesis (DNA replication), occurs before mitosis, as a biological process in all living organisms.
• DNA replication occurs during the S phase of the cell cycle.
• Results in a double-stranded molecule that synthesizes to produce two new molecules from each original strand.

• Semiconservative Replication: Produces two copies, each containing one original and one new strand.
• Replication begins at specific sites on the DNA molecule called origins of replication with its specific sequence of bases (and uses origin)
• Mammalian DNA have many origins

DNA Replication forks

• The replication forms within the nucleus during DNA replication is created by Helicases that break the by bonds holding the ends together
• The replication forks are held together by two single DNA strands

DNA Replication process.

• Replication fork is where the parental DNA strands hasn't untwist, Replication bubbles speed replication up and untwisted DNA is attacked by enzymes while replicating.
• DNA replication involves the leading and lagging strand: -Helicase unwinds the double stranded DNA (dsDNA) for replication making a forked structure -Primase generates a short short strands of RNA that initiaties DNA synthesis, added by DNA, which can only work in the 5'-3' direction and lags on the other strand

DNA Replication:

• Leading strand: new strand DNA synthesized continuously
• Lagging strand: new strand DNA synthesized discontinuously

DNA Polymerase and Other Important Enzymes Participating in DNA Replication

• Main Enzymes and functions in replication of eukaryiotic during cell division: -DNA HelicaseAlso known as the :Destabilizes and unwinds the DNA duplex at the Replication fork, -DNA Polymerase duplex: Builds a new duplex DNA, proof-reading with direction 5' to 3' -Single Strand builds the DNA -:Binds to single starnd and prevents reannealing -Topoisomerase: from supercoiled Nature -DNA Ligasere-aaneals: Fragments of RNA to begin synthesis of new DN

Enzymes that participate in DNA Replication

• Helicase separates strands
• Binding proteins keep strands separate
• Primase makes a short stretch of RNA on the DNA template.
• DNA polymerase adds DNA nucleotides to the RNA primer
• DNA polymerase proofreading checks and replaces Incorrect bases
• Continuous strand synthesis continues in a 5' to 3' direction and joins Okazaki fragments for lagging strands.

Further enzymes that participate in DNA Replication

• Three DNA polymerases (I, II, and III) purified from E. coli function in gaps (Polymerase 1) and repairs (Polymerase 2) and catalyses (Polymerase 3)
• The rate nucleotide additions in Mammals add 50 bases/second while in bacteria at 500 bases/second.

Cell Cycle

• The cell cycle is a cycle of division and event that leads to duplication of DNA producing two daughter cells in stages:

Phase stages of Cell Cycle:

• G1 is gap phase where the begins immediatly aftermitosis, synthesising RNA, protein and Organelles
• S phase is where DNA is replicated to from sister chromatids using Mitochondria, precursor cells made
• G2 Gap phase where precursor cells are made
• Mititiosis with Prophase condensation of chromosomes and and then disapears in centiroles
• Metaphase is a middle line for fibers
• Anaphase separates and reache poles and New envelope are formed
• Telophase for chromosomes to reach poles and decondense. Cytokinesis is division of new phase

Cell Cycle Phases

• Cell Cycle : Many cells haveresting phase, G1, replicates and goes into 6-12hrs, S and growth G2 and DNA makes division
• All phases are 11h,8 h, h and 1 h,repectively.
• The replicated chromosome has two sister chromatids with its DNA.

Cell Cycle

• The chromosomes have diploid cells have two sets that have have somatic
• Haploid that has on ehte which eggs
• Diploid call divide by Mitosis for a new cell to replicate DNA for new cell copy