1 Sylvia S Mader Immagini e concetti della
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Sylvia S. Mader Immagini e concetti della biologia 2 a ed. 2 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
B 4 - Molecular biology 3 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA and inheritance Fredrick Griffith’s experiments with Streptococcus pneumoniae (1931) demonstrated that a “transforming substance” was used as replicator. 4 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA and inheritance Alfred Hershey and Martha Chase (1952) used the T 2 bacteriophage and Escherichia coli for their experiments. 5 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA and inheritance Hershey and Chase showed that DNA, not proteins, enters bacterial cells and directs the phage reproduction. Hershey and Chase’s first experiment - virus DNA is labeled. 6 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA and inheritance Hershey and Chase showed that DNA, not proteins, enters bacterial cells and directs the phage reproduction. Hershey and Chase’s second experiment - virus capsid is labeled. 7 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Nucleic Acids DNA is a polynucleotides (polymers of nucleotides). Each nucleotide is composed of three parts: • a C 5 sugar called deoxyribose; • a phosphate group; • a nitrogen-containing base. 8 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Nucleic Acids There are four possible nitrogen bases. Adenine (A) and guanine (G) have a double-ring structure and belong to a group called purines. Thymine (T) and cytosine (C) have a single-ring structure and are called pyrimidines. 9 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Nucleic Acids RNA (ribonucleic acid) contains a C 5 sugar called ribose and the bases A, C, G. Uracil (U) replaces T. 10 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA is a functional genetic material as it: • varies between species and individuals • can store information • remains constant within a species • replicates • undergoes mutations 11 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA structure DNA is composed by a double strand of nucleotides where C always pairs with G and T pairs with A. 12 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA structure James Watson and Francis Crick constructed the first model of DNA using Rosalind Franklin and Maurice Wilkins’s X-ray diffraction data. 13 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA structure In Watson and Crick double helix model weak hydrogen bonds between the bases hold the two chains to one another. 14 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA is suitable for replication DNA duplication (or replication) is semiconservative as each new filament contains an old strand a new strand. 15 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA is suitable for replication DNA duplication involves three steps: 1. Unrolling and unwinding; 2. Complementary base paring; 3. Joining. DNA polymerase is an enzyme that assists steps 2 and 3. 16 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA is suitable for replication In the C 5 deoxyribose, carbons are numbered 1', 2', 3', 4', and 5' to distinguish from the atoms of the nitrogen base ring. The 5' carbon binds to the P-group. The P-group of a nucleotide is bonded to the 3' C of the adjacent nucleotide. 17 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA polymerase adds nucleotides to the 3' end of the DNA and needs a primer to start the replication of a strand. Telomeres are special noncodifying repetitive nucleotide sequences. 18 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
DNA replication The second strand of DNA is duplicated in opposite direction of the replication fork. Replication is continuous for the leading strand but discontinuous for the lagging strand. 19 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Genes and protein synthesis Genes are expressed by proteins. The “one gene one protein” hypothesis is based on the observation that a defective gene causes a defective enzyme. 20 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Protein synthesis The making of a protein requires two steps. 1. Transcription: DNA is transcribed into m. RNA. 2. Translation: the transcript m. RNA directs the amino acid sequence. 21 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Genetic code The genetic code is the set of information encoded in DNA that is translated into amino acid sequences. A three-nucleotides codon (i. e. AUC) in a sequence specifies a single amino acid. With few exceptions, the genetic code is universal. 22 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Transcription During transcription, complementary base pairing occurs, RNA polymerase joins bases and the coded information passes from the gene to the m. RNA. 23 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Transcription In eukaryotes, exon is a DNA sequence that will be expressed while intron is DNA that has regulatory function but it will not be expressed. Both introns and exons are transcript to primary m. RNA. 24 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Translation Amino acids are transferred by t. RNA (transfer) to the cytoplasm where m. RNA is translated into proteins. t. RNA’s anticodon base-pairs with m. RNA’s codon. 25 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Ribosomes Translation occurs at ribosomes in the cytoplasm. A ribosome has a binding site for m. RNA and three binding sites for t. RNA. 26 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Polypeptide synthesis occurs as a ribosome moves down m. RNA. A polyribosome is a complex of ribosomes translating the same m. RNA. 27 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Polypeptide synthesis: I step Initiation begins the process of polypeptide synthesis. The starting codon is UAG. The ribosome t. RNA binding sites are: E (exit) site, P (peptide) site and A (amino acid) site. 28 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Polypeptide synthesis: II step During elongation, a t. RNA at the P site passes a peptide to an amino acid-carrying t. RNA at the A site. Then translocation occurs: the ribosome moves forward and elongation the peptide bearing t. RNA is at the P site. The used t. RNA exits from the E site. translocation Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019 29
Gene expression The processes of elongation and translocation occur over and over again. At termination, the ribosome reaches a stop codon and the polypeptide is released. Transcription and translation make the gene expression possible. Resume: participants in gene expression 30 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Mutations A mutation is a permanent change in the genomic sequence. It affects the gene expression. • Germ line mutations occur in gametes and can be passed on to offsprings. • Somatic mutations involve body cells and are not transmitted to descendants. Insertions add nucleotides into the DNA, deletions remove one or more nucleotides from the DNA. 31 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Point mutations affect only one or a few nucleotides. Depending on the DNA sequence, those mutations can be harmful or without consequence. 32 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Frameshift mutations involve insertions or deletions of several nucleotides. Frameshift mutations can lead to the expression of a new non-functional protein and cause genetic disorders as the cystic fibrosis. 33 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Transposons Discovered by Barbara Mc. Clintock in 1981. A transposon (or “jumping gene”) is a sequence of DNA that can change position within the chromosome. Transposition can block transcription and be a source of translocation, deletions, inversion or duplication. 34 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Genetic mutations and cancer Apoptosis (programmed cell death) is important in cancer control. • Proto-oncogenes, promote the cell cycle and inhibit apoptosis. • Tumor suppressor genes, protect the cell from the development of the cancer. 35 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Genetic mutations and cancer Oncogenes and mutated tumor suppressor genes cause excess cyclin which stimulates the cell cycle and makes p 53 unavailable so that apoptosis does not occur. 36 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Genetic mutations and cancer Products of faulty genes interfere with signal transduction when cancer develops. A stimulatory signal transduction pathway turns on a proto-oncogene whose products stimulates the cell cycle. 37 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Genetic mutations and cancer When cancer occurs the products of an oncogene leads to overstimulation of the pathway and the cell cycle excellerates. 38 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Genetic mutations and cancer An inhibitory signal transduction pathway turns on a tumor suppressor gene whose products inhibits the cell cycle. 39 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Genetic mutations and cancer When cancer occurs, the product of a mutated tumor suppressor gene fails to turn on the pathway and fails to stop the cell cycle. 40 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Cancer development Carcinogenesis is the development of a malignant tumor due to repeated mutations. 41 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Cancer development Angiogenesis (formation of new blood vessels) provides nutrients to a growing tumor. 42 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Cancer development Motile cells invade lymphatic and blood vessels, metastasis occur when new tumors form far from the original site. 43 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
Cancer therapy Cancer diagnosis includes a complete check of patient health, imagine diagnostics, blood and urine analysis, endoscopy. Surgery of a cancer cell mass is useful only for solid tumors. Chemotherapy is a cancer treatment that uses drugs to destroy cancer cells. Radiotherapy uses high energy rays to destroy cancer cells. 44 Sylvia S. Mader, Concepts of Biology © Zanichelli editore, 2019
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