Overview of DNA Structure and Replication.pdf

9/27/24, 10:26 PM Overview of DNA Structure and Replication DNA Packaging 📦 DNA packaging is the process by which the cell condenses its DNA into a smaller space. The amou...

9/27/24, 10:26 PM Overview of DNA Structure and Replication DNA Packaging 📦 DNA packaging is the process by which the cell condenses its DNA into a smaller space. The amount of DNA in a typical animal cell is approximately 2 meters long, but it must fit into a nucleus that is only 5-10 microns in diameter. Levels of DNA Packaging There are multiple levels of DNA packaging: Histones: proteins that form a complex called the nucleosome, which is the first level of DNA packaging. Nucleosomes: the complex formed by histones, around which DNA is wrapped. Solenoids: structures formed by the coiling of nucleosomes, which is another level of DNA packaging. Control of DNA Packaging The cell can control the condensation of DNA through the acetylation of histones. This process involves the addition of acetyl groups to the lysine amino acids in the histone tails, which eliminates their positive charge and allows the DNA to open up. “"Acetylation of histones is a key mechanism by which the cell regulates gene expression by controlling the accessibility of DNA to transcription factors."” Histone Acetylation Histone Acetylation Effect on DNA Packaging Acetyl groups added to lysine amino acids DNA opens up, allowing for gene expression No acetyl groups DNA remains compact, restricting gene expression Chromatin Structure https://www.turbolearn.ai/content/23cee81e-4af4-4d39-b65c-a230ea9e8c3b 1/11 9/27/24, 10:26 PM Overview of DNA Structure and Replication Type of Chromatin Characteristics Heterochromatin Highly condensed, found at telomeres and centromeres, serves a structural function Euchromatin Less condensed, found in areas with high gene expression RNA Structure 📝 RNA (ribonucleic acid) is a molecule that plays a crucial role in the expression of genes. It is similar to DNA, but with some key differences: Ribose sugar: RNA contains a hydroxyl group at the 2' carbon, whereas DNA contains a hydrogen atom. Uracil: RNA contains uracil instead of thymine. Phosphodiester backbone: RNA has a phosphodiester backbone, which gives it a net negative charge. RNA Pairing Base Pairing RNA DNA Adenine (A) pairs with Uracil (U) pairs with Thymine (T) Guanine (G) pairs with Cytosine (C) pairs with Cytosine (C) Types of RNA Type of RNA Function mRNA carries genetic information from DNA to the ribosome for protein synthesis tRNA brings amino acids to the ribosome for protein synthesis rRNA makes up a large part of the ribosome, which is responsible for protein synthesis 🔄 https://www.turbolearn.ai/content/23cee81e-4af4-4d39-b65c-a230ea9e8c3b 2/11  🔄 9/27/24, 10:26 PM Overview of DNA Structure and Replication DNA Replication DNA replication is the process by which the cell makes an exact copy of its DNA. This process occurs in three stages: initiation, elongation, and termination. Initiation Origin of replication: specific sequences on the DNA that serve as the starting point for replication. ORC (Origin of Replication Complex): a complex that recruits other enzymes necessary for replication. MCM (Mini-Chromosome Maintenance): a complex that helps to unwind the DNA. Elongation Helicase: an enzyme that unwinds the DNA double helix. DNA polymerase: an enzyme that synthesizes new DNA strands. Leading strand: the strand that is synthesized continuously. Lagging strand: the strand that is synthesized in short segments. Termination Replication fork: the region where the DNA is being replicated. Fork 1 and Fork 2: the two replication forks that move in opposite directions. Enzymes Involved in DNA Replication Enzyme Function Helicase unwinds the DNA double helix DNA polymerase epsilon synthesizes the leading strand https://www.turbolearn.ai/content/23cee81e-4af4-4d39-b65c-a230ea9e8c3b 3/11 9/27/24, 10:26 PM Overview of DNA Structure and Replication Enzyme Function DNA polymerase alpha and delta synthesize the lagging strand Topoisomerase and Torsional Stress Topoisomerase is an enzyme that relieves torsional stress on the DNA molecule during replication. As the replication machinery moves down the DNA molecule, it causes the double helix to wind up, leading to torsional stress. Topoisomerase cuts one strand of the DNA, allowing the molecule to unwind and relieving the stress. Leading and Lagging Strands During DNA replication, one strand is synthesized continuously (the leading strand), while the other strand is synthesized in short, discontinuous fragments (the lagging strand). The leading strand is synthesized in the 5' to 3' direction, while the lagging strand is synthesized in the opposite direction. Synthesis Strand Direction Characteristics Leading 5' to 3' Continuous synthesis Strand Lagging 3' to 5' Discontinuous synthesis, synthesized in short fragments Strand (Okazaki fragments) Okazaki Fragments Okazaki fragments are short, discontinuous fragments of DNA synthesized on the lagging strand during replication. They are typically 1000-2000 nucleotides in length and are synthesized in the 5' to 3' direction. RNA Primers https://www.turbolearn.ai/content/23cee81e-4af4-4d39-b65c-a230ea9e8c3b 4/11 9/27/24, 10:26 PM Overview of DNA Structure and Replication RNA primers are short RNA molecules that are added to the lagging strand to provide a 3' hydroxyl group for DNA polymerase to extend. They are necessary because DNA polymerase cannot initiate synthesis de novo. DNA Polymerase DNA polymerase is an enzyme that synthesizes new DNA strands by adding nucleotides to a template strand. It can only add nucleotides to a 3' hydroxyl group, which is why RNA primers are necessary for lagging strand synthesis. PCNA (Proliferating Cell Nuclear Antigen) PCNA is a protein complex that acts as a sliding clamp, holding DNA polymerase onto the DNA template during replication. It increases the processivity of DNA polymerase, allowing it to synthesize longer stretches of DNA. Termination of Replication Replication is terminated when the replication machinery reaches the end of the chromosome. The leading strand is synthesized continuously until the end of the chromosome, while the lagging strand is synthesized in short fragments that are later joined together. Telomeres and Telomerase Telomeres are the ends of chromosomes, which are protected by repetitive DNA sequences. Telomerase is an enzyme that extends the lagging strand of the telomere, allowing for the replication of the telomere. Mutations 🧬 Definition “A mutation is a change in the DNA sequence of an organism. It can occur spontaneously or be induced by external factors.” Types of Mutations https://www.turbolearn.ai/content/23cee81e-4af4-4d39-b65c-a230ea9e8c3b 5/11 9/27/24, 10:26 PM Overview of DNA Structure and Replication Spontaneous mutations: occur randomly and naturally Induced mutations: occur due to external factors such as radiation or chemicals Depurination Depurination is a type of spontaneous mutation that occurs when a purine base (adenine or guanine) is lost from the DNA molecule. This can lead to a deletion or substitution mutation. Type of Mutation Description Deletion Loss of one or more nucleotides Substitution Replacement of one nucleotide with another Consequences of Mutations Mutations can have varying effects on the cell, depending on the location and type of mutation. They can: Have no effect on the cell Affect the function of a gene Cause a change in the amino acid sequence of a protein## Mutations 🧬 Mutations are changes in the DNA sequence of an organism. They can occur spontaneously or be induced by external factors. Types of Mutations Point Mutations: A change in a single nucleotide in the DNA sequence. Insertions: The addition of one or more nucleotides to the DNA sequence. Deletions: The removal of one or more nucleotides from the DNA sequence. https://www.turbolearn.ai/content/23cee81e-4af4-4d39-b65c-a230ea9e8c3b 6/11 9/27/24, 10:26 PM Overview of DNA Structure and Replication Trinucleotide Expansions: A type of mutation where a sequence of three nucleotides is repeated multiple times. Chromosomal Translocations: A type of mutation where a piece of a chromosome breaks off and attaches to another chromosome. Spontaneous Mutations Spontaneous mutations occur naturally and can be caused by errors during DNA replication or repair. Examples include: Depurination: The loss of a purine base (adenine or guanine) from the DNA sequence. Deamination: The loss of an amino group from a cytosine base, resulting in the formation of uracil. “"Depurination and deamination are examples of spontaneous mutations that can occur in DNA. These mutations can be caused by errors during DNA replication or repair."” Induced Mutations Induced mutations are caused by external factors, such as: Chemicals: Certain chemicals can cause mutations by altering the DNA sequence. Ultraviolet (UV) Light: UV light can cause the formation of pyrimidine dimers, which can lead to mutations. X-rays: X-rays can cause double-strand breaks in DNA, leading to mutations. Trinucleotide Expansions Trinucleotide expansions occur when a sequence of three nucleotides is repeated multiple times. This can lead to the formation of abnormal proteins. https://www.turbolearn.ai/content/23cee81e-4af4-4d39-b65c-a230ea9e8c3b 7/11 9/27/24, 10:26 PM Overview of DNA Structure and Replication Repeated Normal Repeat Disease-Associated Disease Sequence Number Repeat Number Huntington's CAG 28 or fewer 40 or more Disease Chromosomal Translocations Chromosomal translocations occur when a piece of a chromosome breaks off and attaches to another chromosome. Type of Translocation Description Balanced Translocation A piece of a chromosome breaks off and attaches to another chromosome, without any loss of genetic material. Unbalanced A piece of a chromosome breaks off and attaches to another Translocation chromosome, resulting in a loss of genetic material. DNA Repair Mechanisms 🧬 DNA repair mechanisms are essential for maintaining the integrity of the genome. Excision Repair Excision repair is a type of DNA repair that involves the removal of damaged DNA and its replacement with new DNA. Type of Excision Repair Description Nucleotide Excision Repair The removal of damaged nucleotides and their replacement with new nucleotides. Base Excision Repair The removal of damaged bases and their replacement with new bases. https://www.turbolearn.ai/content/23cee81e-4af4-4d39-b65c-a230ea9e8c3b 8/11 9/27/24, 10:26 PM Overview of DNA Structure and Replication “"Excision repair is a type of DNA repair that involves the removal of damaged DNA and its replacement with new DNA."” Mismatch Repair Mismatch repair is a type of DNA repair that involves the correction of errors in DNA replication. Step Description Recognition The recognition of mismatched bases in the DNA sequence. Excision The removal of the mismatched bases. Repair The replacement of the mismatched bases with the correct bases. Proteins Involved in DNA Repair Protein Function XPABC Involved in nucleotide excision repair. MSH2 Involved in mismatch repair. “"DNA repair mechanisms are essential for maintaining the integrity of the genome. Errors in DNA repair can lead to genetic diseases and cancer."## DNA Repair Mechanisms 🧬” Mismatch Repair and Hereditary Cancers MSH2 and MLH1 are genes commonly mutated in Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer, HNPCC) Individuals with Lynch syndrome have a high risk of colon cancer and other cancers due to mutations in genes important for mismatch repair Double-Strand Break Repair https://www.turbolearn.ai/content/23cee81e-4af4-4d39-b65c-a230ea9e8c3b 9/11 9/27/24, 10:26 PM Overview of DNA Structure and Replication A double-strand break is a type of DNA damage where both strands of the DNA molecule are broken. There are two ways to repair double-strand breaks: Non-Homologous End Joining (NHEJ) 🔩 “Non-homologous end joining is a type of DNA repair mechanism that involves the direct ligation of broken DNA ends without the need for a template.” Occurs in G1 cells (non-cycling cells) or somatic cells Involves the removal of nucleotides from the broken ends, which can lead to mutations Uses enzymes such as Ku70 to recognize and repair double-strand breaks Considered a "quick and dirty" method of repair, but can introduce mutations Homologous Recombination (HR) 🔗 “Homologous recombination is a type of DNA repair mechanism that uses a template with a similar sequence to repair the damaged DNA.” Occurs in cells that have gone through S phase and have two copies of each chromosome Uses the non-mutated copy of the chromosome as a template to repair the damaged DNA Considered an error-free mechanism of repair Involves the use of enzymes such as ATM to initiate the repair process ATM and DNA Repair Description ATM A gene that plays a crucial role in initiating the repair of double-strand breaks through both non-homologous end joining and homologous recombination https://www.turbolearn.ai/content/23cee81e-4af4-4d39-b65c-a230ea9e8c3b 10/11 9/27/24, 10:26 PM Overview of DNA Structure and Replication Description Ataxia A genetic disorder caused by mutations in the ATM gene, leading to an Telangiectasia increased susceptibility to DNA damage and cancer Individuals with ataxia telangiectasia are at risk of accumulating mutations due to their inability to repair double-strand breaks ATM is important for both non-homologous end joining and homologous recombination, making it a critical gene for DNA repair DNA Polymerases Different types of DNA polymerases exist, with varying nomenclature (e.g. Greek letters, numbers) The relationship between Greek letters and numerical nomenclature is unclear and may depend on the specific source or context https://www.turbolearn.ai/content/23cee81e-4af4-4d39-b65c-a230ea9e8c3b 11/11