Genes that Regulate the Cell Cycle, Transcription, mRNA Transcripts, Translation, Mutations that Affect Gene expression
Genes that Regulate the Cell Cycle, Transcription, mRNA Transcripts, Translation, Mutations that Affect Gene expression BIOL 121N
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This 17 page Bundle was uploaded by Dominick Ramos on Monday October 19, 2015. The Bundle belongs to BIOL 121N at Old Dominion University taught by DOUGLAS J MILLS in Fall 2015. Since its upload, it has received 29 views. For similar materials see GENERAL BIOLOGY I in Biological Sciences at Old Dominion University.
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Biol121NCancer Biology Genes That Regulate the Cell Cycle An allele is an alternative form of a single gene Each allele 0 Has a unique nucleotide sequence 0 Contains different genetic information There are an alleles for the average gene in the human population The definition of a mutation Mutation a change in the nucleotide sequence of a DNA molecule or the RNA genome of RNA viruses The definition of a mutagen A mutagen causes a mutation in a DNA molecule or the RNA genome of RNA viruses Mutagens can be 0 Biological chemical or physical Protooncogenes regulate the cell cycle Protooncogenes code for proteins that regulate the cell cycle and thus cell division in a controlled manner 0 They stimulate the cell cycle and promote cell division in a regulated manner Protooncogenes can code for o Gosignals o Gosignal receptors 0 G proteins 0 Cyclin proteins 0 Kinases o Enzymes that synthesize nucleotides Some mutations convert a protooncogene to an oncogene A can convert a promoncogene to an 0 An oncogene codes for a new protein oncoprotein that stimulates cell division in an unregulated manner Copyright 2015 Dominick Ramos All Rights Reserved Biol121NCancer Biology Genes That Regulate the Cell Cycle Tumor suppressor genes regulate the cell cycle Tumor suppressor genes code for proteins that Are necessary for cell division to occur in a regulate manner Ensure that cell division occurs accurately Slow or inhibit cell division in a regulated manner Detect DNA damage mutation Repair DNA mutations Form cell cycle checkpoints Enable apoptosis to occur Allow proper cell to cell binding Allow proper cell binding to the extracellular matrix Some mutations inactivate tumor suppressor genes A loss of function mutation in a tumor suppressor gene eliminates its ability to code for a functional protein that can result in Failure of cell cycle checkpoints Failure to recognize and repair mutations in DNA Failure to induce apoptosis Metastasis Copyright 2015 Dominick Ramos All Rights Reserved Biol121NCancer Biology Genes That Regulate the Cell Cycle TODAY S STUDY GUIDE QUESTIONS WHAT IS AN MUTATION MUTAGEN CARCINOGEN ALLELE CAN CARCINOGENS CAUSE CANCER BY CAUSING MUTATIONS IN PROTOONCOGENES OR TUMOR SUPPRESSOR GENES WHAT IS THE NORMAL ROLE OF PROTOONCOGENES IN CELL CYCLE REGULATION WHAT ARE SOME EXAMPLES OF PROTOONCOGENES WHAT TYPE OF MUTATION CAN CONVERT A PROTOONCOGENE TO AN ONCOGENE WHY DOES AN ONCOGENE SlGNlFlCANTLY INCREASE THE RISK OF CANCER WHAT IS THE NORMAL ROLE OF TUMOR SUPPRESSOR GENES IN CELL CYCLE REGULATION WHAT ARE SOME EXAMPLES OF TUMOR SUPPRESSOR GENES WHAT TYPE OF MUTATION CAN INACTIVATE A TUMOR SUPPRESSOR GENE THERE ARE MULTIPLE ALLELES OF EACH PROTOONCOGENE AND TUMOR SUPPRESSOR GENE IN THE HUMAN POPULATION DO THE ALLELES THAT AN INDIVIDUAL HAS AT A SPECIFIC PROTOONCOGENE OR SPECIFIC TUMOR SUPPRESSOR GENE AFFECT THE RISK OF CANCER Copyright 2015 Dominick Ramos All Rights Reserved BiollZlNTranscription 1 The onegene one Mptide hypothesis One gene determines the amino acid sequence of one polypeptide o the sequence of nucleotides in the gene determines the sequence of amino acids in the polypeptide that the gene encodes Each of the 46 DNA molecules in the nucleus contains many genes The linear sequence of triplets in the gene determines the linear sequence that the polypeptide encodes The genetic code the genetic language It is the set of rules that store genetic instructions in NDA and in mRNA molecules 0 based on quotgenetic words called triplets 0 each nucleotide ACGT is a letter of the quotgenetic alphabet 0 each triplet consists of in a gene that codes for 0 specific amino acids 0 start signals 0 stop signals The genetic code is universa All biological systems us the same system to 0 store genetic information in genes 0 access the genetic information in genes to make every protein and specialized RNA molecule they require Defining gene expression The precise activation and deactivation of genes The multistep process that converts the information stored in a gene into a specific protein in the proper cell type at the proper time at the proper concentration The transcription process It transfers the triplet code information stored in the coding strand of a gene to a messenger RNA mRNA molecule or transcript Transcription in eukaryotic cells It occurs in o the nucleus and mitochondria in animals Biol121NTra nscription o in the nucleus mitochondrion and chloroplasts of plant cells and algal cells RNA polymerase make mRNA during transcription RNA polymerase is the enzyme that o joins ribonucleotides together to make mRNA 0 reads the nucleotide sequence of the template strand of a gene to make a complementary mRNA with a sequence identical to the coding strand 0 replaces T with U in the mRNA molecules transcripts it makes RNA polymerase begins reading the nucleotide sequence of the template strand of a gene at the The initiation phase of transcription RNA polymerase and the assemble at the promoter region during the initiation phase to form the transcription preinitiation The elongation phase of transcription RNA polymerase o unwinds the double helix quot1020 base pairs at a time to read the nucleotide sequence of the template strand 0 makes an mRNA molecule with a sequence complementary to the template strand and identical to the coding strand 0 joins 50 ribonucleotides together per second The termination phase of transcription When RNA polymerase encounters the polyadenlyation signal ATAAA or transcription stop site it releases the mRNA molecule transcript BiollZlNTranscription TODAY S STUDY GUIDE QUESTIONS 1 WHAT IS THE GENETIC CODE a WHAT IS A TRIPLET b WHAT IS A CODON c DO ALL LIFE FORMS USE THE SAME GENETIC CODE 2 WHAT SPECIFIC INFORMATION IS STORED IN A GENE 3 WHAT IS TRANSCRIPTION 4 DURING THE TRANSCRIPTION PROCESS WHICH EVENTS OCCUR IN THE a INITIATION PHASE b ELONGATION PHASE c TERMINATION PHASE 5 WHAT IS A PROMOTER IS THE TATA BOX SEQUENCE IN THE PROMOTER 6 TO WHICH SEQUENCE DO RNA POLYMERASE H AND THE SIX GENERAL TRANSCRIPTION FACTORS BIND DURING THE INITIATION PHASE 7 THE SIX GENERAL TRANSCRIPTION FACTORS ALIGN AND ACTIVATE RNA POLYMERASE ON THE REGION OFAGENE 8 WHICH MOLECULE IS SYNTHESIZED BY RNA POLYMERASE DURING THE ELONGATION PHASE OF TRANSCRIPTION BiollZlNTranscription 9 MESSENGER RNA IS AN EXACT COPY OF WHICH STRAND OF THE GENE EXCEPT THAT URACIL REPLACES THYMINE 10 WHICH STRAND OF A GENE DOES RNA POLYMERASE quotREADquot DURING TRANSCRIPTION Biol121NMutations That Affect Gene Expression 1 Some mutations affect gene expression 0 Mutations in the promoter can affect transcription 0 Mutations in the splicing sites can affect splicing o Mutations in the start and stop codons can affect translation Mutations can change the instructions in a gene A change in the nucleotide sequence of an exon of a gene can result in the gene coding for a protein with a different amino acid sequence This can alter the structure of a protein causing o A change in its function 0 The elimination of its function Point mutations 0 An addition point mutation one nucleotide pair 0 A deletion point mutation one nucleotide pair 0 A substitution point mutation one nucleotide pair with another Silent Svnonvmous Point Mutations A change in the nucleotide of the codon the amino acid encoded by the codon o The altered codon codes for the same amino acid Missense Nonsynonymous Point Mutations A new codon is formed that codes for a different amino acid 0 Conservativethe altered codon codes for a chemicallysimilar amino acid that is to change protein function 0 Nonconservativethe altered codon codes for a chemicallydissimilar amino acid that is to change protein function Nonsense Point Mutations A codon that codes for an amino acid is changed to one of the three stop codons UAA UAG or UGA o Nonsense point mutations that significantly reduce protein length typically eliminate protein function BiollZlNMutations That Affect Gene Expression 2 Frameshift Point Mutations The addition or deletion of one nucleotide pair alters the quotreading frame of a gene They usually eliminate protein function because 0 All codons downstream from the mutation site are changed 0 A premature stop codon frequently is formed Chromosome abnormalities 0 Deletionan entire group of genes is removed from a chromosome 0 Duplicationan entire group of genes is copied duplicated in a chromosome 0 Inversionan entire group of genes is inverted flipped in a chromosome 0 Translocationan entire group of genes is exchanged between chromosomes Nondisjunction during meiotic cell division results in sperm and egg with abnormal chromosome number not 23 o Aneuploidy the nucleus of a cell contains of chromosomes not 46 in human cells 0 Polyploidy the nucleus of a cell contains complete sets of chromosomes Genetic disorders due to chromosome abnormalities 0 Down syndrome trisomyoccurs in X21 o Kinefelter Syndrome XXYXYY Synd romeoccu rs in sex chromosomes normalXY abnormalXXY or XYY o Turner syndrome XOtypically inherited from the mother normalXX abnormalX0 Mutation is the source of in populations Some mutations increase the ability of an individual to reproduce in its current environment and consequently increase in frequency in future generations Biol121NmRNA Transcripts The addition of the 5 GCap to the 5 end of the mRNA The attaches a to form the 5 Gcap o This process occurs during transcription The addition of the 3 PolvA tail to the 3 end of the mRNA is the enzyme that attaches 50250 adenine nucleotides to the 3 end of mRNA to form the 3 polyA tail 0 This process occurs in the nucleus after transcription 0 The polyA tail can be added to different sites in the mRNA molecule to produce more than one type of mRNA from a single gene The functions of the 5 GCmnd the 3 PolvA tai These molecules 0 Enable the export of mRNAs from the nucleus to the cytoplasm 0 Enable mRNAs to interact with ribosomes in the cytoplasm so they can be translated o Prevent premature mRNA degradation mRNA molecules are spliced in eukaryotic cells mRNA splicing occurs within the nucleus after transcription The spliceosome removes introns from the mRNA and joins the remaining exons together during splicing o Splicing is a quotcut amp paste job 0 Some introns are ribozymes that can remove themselves from mRNA 0 Any nucleotide sequence removed from mRNA during splicing is an intron Alternative splicing Alternative splicing enables mRNA transcripts with different nucleotide sequences to be produced from one gene 0 This enables different versions of a protein to be produced from one gene 0 Each version of the protein is specialized for a specific 0 Cthype 0 Stage of development 0 Environmental condition Biol121NmRNA Transcripts 2 BThalassemia Affects quot1 in 100000 Individuals This genetic disorder is caused by the abnormal splicing of Bglobin mRNA 0 Fewer blood cells are produced causing severe anemia 0 Red blood cells have reduced BGlobin levels 0 Blood transfusions are required every 23 weeks Eukarvotic cells benefit from mRNA processing Alternative splicing allows one gene to produce 0 Specialized versions of a protein 0 Proteins that have completely different cellular functions The risk of infection is reduced because unprocessed foreign mRNAs viral mRNAs would 0 Not be exported from the nucleus and therefore could not contact the ribosomes 0 Not be recognized by ribosomes and therefore not be translated to produce viral proteins 0 Be degraded by RNases and eliminated from the cell Alternative splicing Alternative splicing enables one gene to code for two or more proteins that have significantly different cellular functions Eg the genes that code for the aminoacyl transfer RNA synthetases also can code for proteins with significantly different cellular functions Alternative splicing enables our cells to produce hundreds of thousands of different proteins from our quot20000 proteincoding genes The medical consequences of abnormal splicing Abnormal splicing of the mRNA transcribed from a protooncogene or a tumor suppressor gene hypothetically could increase the risk of cancer BiollZlNmRNA Transcripts BiollZlNTranslation 1 The translation of messenger RNA mRNA 0 Mature processed mRNA transcripts are exported from the nucleus through the to the cytosol o Ribosomes in the cytosol translate the genetic code information in a processed mRNA to make a polypeptide protein with a specific amino acid sequence 0 The sequence of codons in the mRNA determines the sequence of amino acids in the polypeptide produced during translation The ribosome performs translation Each ribosome consists of a large subunit and a small subunit 0 Each subunit consists of ribosomal RNA rRNA and ribosomal proteins The cellular function of transfer RNA tRNA tRNAs deliver amino acids to the ribosome during translation 0 Each of the has a specific tRNA molecule that delivers it to the ribosome The aminoacvltRNA svnthetases These enzymes link the proper amino acid to the proper tRNA 0 There are of this enzyme 0 There is one version for each of the 20 types of amino acids Codons and the genetic code 0 A is a 3nucleotide sequence or quotgenetic word in the gene 0 A is a 3nucleotide sequence or quotgenetic word in the messenger RNA 0 The triplet in the gene is called a codon in the mRNA 0 Most codons code for a specific amino acid 0 One codon codes for the translation start site 0 Three codons code for the translation stop site BiollZlNTranslation THE GENETIlC CODE TABLE Second mRNA base EACH CODOlN THAT 7 iii CODES FOR AN Ammo quotUquot Pm 390 AUJTW 39 U ACID CODES FOR ONLY L UUC CC Se UAC 393 DNE AMIIIlN D AClID UUA Le USA A unue 39 UCG A G E E C E A s a 9 SOME AMIIND ACIDS HAVE g CU CCU CA U His CGU U E MlO E THAlN ONE CODDH c GUC L CBC Pro CAGE EGG A C 7 z A T W E CUA E CCA CAA 7 BSA 9 A E a 7 GI V V lillll in clue CCE CAG g EGG G 23 Auu Acu AAu AGLl u g 7 7 7 Asn 7 Ser 41 q AUC Ile ACC AAC AGC C A z A 7 TM 7 2 l ALIA ACA AAA 7 AGA 7 A If E 7 Lys Arg E 5 AUG 331 ACG AAC 2 AGO G E 9 F I e THE FIRST AND SECOND u39l Guu Ge GAU SA GGU u 39 v l l 539 NUCLEOTIDE IN A CODON G Gm Gcc GAG F Gee GI c I H l 39 V I 1 OFTElN DETERMINE THE GM a GM Ala GM Gm V A AMINO ACID I39I39 ENCODES Gm GOG W G GAG GGG The initiation phase of translation 0 All parts of the translation initiation complex are assembled correctly aligned and activated 0 GTP is required as an energy source to assemble both ribosomal subunits the mRNA the tRNA that recognizes the start codon and to activate the ribosome o Initiation factors are proteins that o Assemble align and activate the ribosome o Unwind mRNA so it can interact with the ribosome The precise interaction between tRNAs and codons Each tRNA recognizes the proper between the proper tRNA amp the proper codon in the mRNA during translation The elongation cycle of translation The polypeptide protein is synthesized during elongation cycle 0 Amino acids are linked together by an enzyme in the ribosome o GTP is required as an energy source 0 Elongation factors are proteins required for the o Proofreading of the tRNAs before they enter the ribosome o Ribosome to move relative to the mRNA so it can read the next codon BiollZlNTranslation Peptidvl transferase is a ribozvme The enzyme peptidyl transferase 0 Links the amino acids together during the elongation cycle o Is the 285 rRNA molecule in the large ribosomal subunit The termination phase of translation The release factor interacts with the stop codon to instruct the ribosome to stop making the polypeptide protein and release the o Polypeptide 0 mRNA so it can be translated by other ribosomes GTP is required as an energy source Some antibiotics inhibit translation Some antibiotics destroy pathogenic bacteria by preventing their 70 S ribosomes from making proteins Ribosomes are synthesized in the in the BiollZlNTranslation 4 TODAY S STUDY GUIDE QUESTIONS 0 WHICH PROCESS CONVERTS THE INFORMATION IN mRNA INTO A SPECIFIC POLYPEPTIDE PROTEIN WITH A SPECIFIC AMINO ACID SEQUENCE WHERE DOES THIS PROCESS OCCUR IN EUKARYOTIC CELLS ARE ALL RIBOSOM ES FORMED FROM A SMALL SUBUNIT AND A LARGE SUBUNIT DESCRIBE EACH STAGE OF TRANSLATION WHICH SOURCE OF ENERGY DRIVES EACH STAGE WHICH PROTEINS ARE REQUIRED FOR EACH STAGE 0 WHICH TWO TYPES OF BIOLOGICAL MOLECULES INTERACT TO FORM THE SMALL AND LARGE RIBOSOMAL SUBUNITS WHICH SPECIALIZED TYPE OF RNA DELIVERS THE AMINO ACIDS TO THE RIBOSOME DURING TRANSLATION WHICH FAMILY OF ENZYMES LINKS THE PROPER AMINO ACID TO THE PROPER tRNA 0 HOW DOES THE PROPER tRNA RECOGNIZE THE PROPER CODON IN THE mRNA DURING TRANSLATION WHICH ENZYME IN THE LARGE RIBOSOMAL SUBUNIT LINKS THE AMINO ACIDS TOGETHER DURING TRANSLATION 0 HOW DOES THE NEWLY FORMED PROTEIN EXIT THE RIBOSOME AS IT IS BEING SYNTHESIZED BiollZlNTranslation WHICH PROTEIN IS REQUIRED TO END TERMINATE TRANSLATION 0 WHAT ARE SOME ANTIBIOTICS THAT KILL BACTERIA BY INHIBITING TRANSLATION AND CONSEQUENTLY PREVENTING PROTEIN SYNTHESIS
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