DNA, Chromosome &DNA Replication Lecture Notes PDF

Republic of Iraq Ministry of Higher Education :Stage and Scientific Research :Module Wasit Universty College of medicine :Lecture Title DNA, Chromosome &DNA replication Lecturer Name: Dr-Dhamyaa Alsarray  Nucleic Acids: DNA and R...

Republic of Iraq Ministry of Higher Education :Stage and Scientific Research :Module Wasit Universty College of medicine :Lecture Title DNA, Chromosome &DNA replication Lecturer Name: Dr-Dhamyaa Alsarray  Nucleic Acids: DNA and RNA Nucleic acids: are linear polymers of nucleotides ‘polynucleotides’ that required for the storage and expression of genetic information. There are two chemically distinct types of nucleic acids: ❖Deoxyribonucleic acid (DNA) ❖Ribonucleic acid (RNA)  Nucleic Acids: DNA and RNA DNA: is polymer of deoxyribonucleotides covalently linked by 3‫׳‬5→‫ ׳‬phosphodiester bond carrying the genetic information in all cellular forms of life and some viruses. RNA: is polymer of ribonucleotides covalently linked by 3‫׳‬5→‫׳‬ phosphodiester bond that function as an intermediary in the transfer of genetic information from DNA to protein Nucleotides: Building blocks of nucleic acids Nucleotides: are basic building block of DNA and RNA Each nucleotide consists of three components: a nitrogenous base, a pentose sugar and a phosphate molecule Nucleoside composed of only : a nitrogenous base and a pentose sugar Nucleotides components 1-Nitrogenous base: There are two types Purine: have a two-ring structure (Adenine (A) and Guanine (G)) Pyrimidine: have a one-ring structure (Thymine (T) Cytosine (C) and Uracil (U) DNA has A,G,T,C and RNA has A,G,U,C Adenine Cytosine Uracil (in RNA) Thymine (in DNA) Guani ne Nucleotides components Note the similarity between the 6-membered rings Also that these structures are ‘planar’ (it can be represented on a flat surface) because of the double bonds, and unsaturated Nucleotides components 2-Pentose sugar: There are two types Ribose in RNA 2-Deoxyribose in DNA 5 5 H HO 4 1 O4 1 3 2 3 2 3-A phosphate group: The phosphate groups are strongly acidic and are the reason DNA and RNA are called acids. Nucleotides structure Nucleotides are formed by covalent bonding of the phosphate, base, and sugar. N-glycocdic bond Phosphate ester bond Nucleotides Nomenclature Deoxyribonucleotide Deoxyadenosine (Nucleoside) Deoxyadenosine monophosphate (dAMP) Deoxyadenosine diphosphate (dADP) Deoxyadenosine triphosphate (dATP) Polynucleotides Nucleotides are covalently linked via 3'→5' phosphodiester bonds to form polynucleotides chains. The resulting chain has polarity, with both a 5'-end (the end with free phosphate) and a 3'-end ( the end with free hydroxyl group) that are not linked to other nucleotides, resulting in chain with 5'→3' direction The bases written in the conventional 5'→3' direction: 5'-AGCT-3‘ DNA has two polynucleotides chains and RNA has only one Each single-strand nucleic acid chain has a polarity The Watson-Crick Model of DNA Structure According to Watson and Crick model (1953) DNA is composed of two polynucleotide chains running in opposite directions (antiparallel), one chain run in 5'→3'direction, the other in 3'→5'direction. The Watson-Crick Model of DNA Structure The two chains are twisted (coiled) around each other in a right-handed to form a double helix. the hydrophilic deoxyribose-phosphate backbone of each chain is on the outside the molecule, whereas the hydrophobic bases are stacked inside where they are paired by hydrogen bonds. The overall structure resembles the twisted ladder. The Watson-Crick Model of DNA Structure Base pairing is highly specific: A in one chain pairs with T in the opposite chain by two hydrogen bonds , and C pairs with G by three bonds. The base pairing of the model makes the two polynucleotide chains of DNA complementary in base composition. If one strand has the sequence 5′-ACGTC-3′, the opposite strand must be 3′-TGCAG-5′, and the double-stranded structure would be written as 5′-ACGTC-3′ 3′-TGCAG-5′ Chargaff Rule (base ratio): A=T , G = C, The Watson-Crick Model of DNA Structure One complete turn is 10 base pairs and space between base pairs is 0.34nm The spatial relationship between the two strands in the helix creates a major (wide) groove and a minor (narrow) groove. The bases in these grooves exposed and therefore interact with proteins or other molecules. The third -OH group on the phosphate is free and dissociates a hydrogen ion at physiologic pH. Therefore, each DNA helix has negative charges coating its surface that facilitate the binding of specific proteins. Important of Watson-Crick Model ✔ Genetic information is stored in the sequence of bases in the DNA, which have a high coding capacity. ✔ The model offers a molecular explanation for mutation. Because genetic information is stored as a linear sequence of bases in DNA, any change in the order or number of bases in a gene can result in a mutation that produces an altered phenotype. ✔ The complementary nature of the two polynucleotide DNA strands helps explain how DNA is copied; each strand can be used as a template to reconstruct the base sequence in the opposite strand, and also the mechanisms of transcription and translation (allows a strand of DNA to serve as a template for the synthesis of a complementary strand of RNA that used to direct the process of protein synthesis).  DNA Denaturation and Renaturation DNA Denaturation & Renaturation : the double strands can separate into single strands by disruption the hydrogen bonds between the paired bases using acidic or alkaline pH or heating. (phosphodiester bond are not broken 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 (deoxyribonucleases), only RNA can be cleaved by alkali  DNA CONDENSATION A cell's genetic information, in the form of DNA, is stored in the nucleus. The space inside the nucleus is limited and has to contain billions of nucleotides that compose the cell's DNA. Therefore, the DNA has to be highly organized or condensed. There are several levels to the DNA packaging. solenoid The DNA coils around proteins called histones, forming a beads-on-a-string-like structure. The bead part is called a nucleosome. It is a little like wrapping a very long, thin piece of thread around your fingers, to keep it from unraveling and tangling. DNA wraps at several levels, until it is compacted into a chromosome.. Specifically, a nucleosome composed of eight histone proteins (a pair of each of four types). A fifth type of histone protein anchors nucleosomes to short “linker” regions of DNA, which then tighten the nucleosomes into fibers 30 nanometers (nm) in diameter. As a result, at any given time, only small sections of the DNA double helix are exposed. To further condense the DNA material, nucleosomes are compacted together to form chromatin fibers. The chromatin fibers condense to form chromosome during cell division.. Packing of DNA into Chromatin  Difference between chromatin and chromosome Chromatin It is uncondensed part of nucleoprotein complex. Chromatin is observable in the interphase nucleus. It is active in controlling metabolism and other activities of the cell.  Chromosomes Chromosomes are condensed parts of the nucleoprotein complex. Chromosomes are observable during M-phase or nuclear division. Chromosomes are mainly meant for distribution of genetic information to the daughter cells.  - Chromosomes are also used as a way of referring to the genetic basis of an organism as either diploid or haploid. Many eukaryotic cells have two sets of the chromosomes and are called diploid. Other cells that only contain one set of the chromosomes are called haploid. A human has 46 chromosomes (2n = 46) And 23 chromosome in haploid cell.  Structure of Chromosomes The centromere is a constricted region of the chromosome containing a specific DNA sequence, to which is bound 2 discs of protein called kinetochores. Kinetochores serve as points of attachment for microtubules that move the chromosomes during cell division. Metaphase chromosome Centromere region of chromosome Kinetochore Kinetochore microtubules Sister Chromatids Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Chromosome structure p: short arm q: long arm C: constriction point or centromere , the location of centromere give the chromosome its shape and can be used to help describe the location of the genes.  In a cell in which DNA synthesis has occurred all the chromosomes are duplicated and thus each consists of two identical sister chromatids. Maternal set of Remember DNA synthesis occur chromosomes (n = 3) before mitosis 2n = 6 Paternal set of chromosomes (n = 3) Two sister chromatids of one replicated chromosome Centromere Two nonsister Pair of homologous chromatids in chromosomes a homologous pair (one from each set)  DNA REPLICATION - DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. - The process starts when one double-stranded DNA molecule produces two identical copies of the molecule. - DNA replication occurs during S phase of the cell cycle  How does DNA replicate? DNA Replication is a semiconservative process that results in a double-stranded molecule that synthesizes to produce two new double stranded molecules such that each original single strand is paired with one newly made single strand. Semiconservative replication would produce two copies that each contained one of the original strands and one new strand. " ,replication begins at specific sites on DNA molecule called "origins of replication origins are specific sequence of bases mammalian DNA have many origins The replication fork is a structure that forms within the nucleus during DNA replication. It is created by helicases, which break the hydrogen bonds holding the two DNA strands together. Replication fork is where the parental DNA strands hasn't untwist. Replication bubbles allow DNA replication to speed up therefore the untwisted DNA would not be attacked by enzymes while replicating.. Steps of replication  Phases of the Cell Cycle Interphase – G1 - primary growth – S - genome replicated – G2 - secondary growth M - mitosis C - cytokinesis