STEP 1 USMLE Questions and Answers with Complete Solutions 2023

TOPIC: BIOCHEMISTRY - MOLECULAR / "CHROMATIN STRUCTURE" WHAT BINDS TO THE NUCLEOSOME AND TO LINKER DNA TO STABILIZE CHROMATIN FIBER? - ANSWER-H1 TOPIC: BIOCHEMISTRY - MOLECULAR / "CHROMATIN STRUCTURE PHOSPHATE GIVES DNA WHAT CHARGE? - ANSWER-NEGATIVE TOPIC: BIOCHEMISTRY - MOLECULAR / "CHROMATIN STRUCTURE WHAT GIVES HISTONES A POSITIVE CHARGE? - ANSWER-LYSINE AND ARGININE TOPIC: BIOCHEMISTRY - MOLECULAR / "CHROMATIN STRUCTURE WHEN DOES DNA CONDENSE TO FORM CHROSOMES? - ANSWER-IN MITOSIS TOPIC: BIOCHEMISTRY - MOLECULAR / "CHROMATIN STRUCTURE WHEN DOES DNA AND HISTONE SYNTHESIS OCCUR? - ANSWER-DURING S PHASE TOPIC: BIOCHEMISTRY - MOLECULAR / "CHROMATIN STRUCTURE DOES MITCHONDRIA HAVE THEIR OWN DNA? - ANSWER-YES TOPIC: BIOCHEMISTRY - MOLECULAR / "CHROMATIN STRUCTURE WHAT IS THE STRUCTURE OF MITOCHRONDRIA? - ANSWER-CIRCULAR AND DOES NOT UTILIZE HISTONES TOPIC: BIOCHEMISTRY - MOLECULAR / "CHROMATIN STRUCTURE WHAT IS HIGHLY CONDENSED WITH BARR BODIES (INACTIVE X CHROMOSOMES), TRANSCRIPTIONALLY INACTIVE, INCREASES METHYLATION AND DECREASES ACETYLATION? - ANSWER-HETEROCHROMATIN TOPIC: BIOCHEMISTRY - MOLECULAR / "CHROMATIN STRUCTURE WHAT IS LESS CONDENSED TRANSCRIPTIONALLY ACTIVE. HINT: EU = TRULY TRANSCRIBED" / EXPRESSED - ANSWER-EUCHROMATIN TOPIC: BIOCHEMISTRY - MOLECULAR / "CHROMATIN STRUCTURE WHAT CHANGES THE EXPRESSION OF A DNA SEGMENT WITHOUT CHANGING THE SEQUENCE, AND IS INVOLVED IN AGING, CARCINOGENESIS, GENOMIC IMPRINTING, TRANSPOSABLE ELEMENT REPRESSION, AND INACTIVATION OF THE X CHROMOSOME? HINT: MAKES DNA MUTE - ANSWER-DNA METHYLATION Removal of histones positive charge, relaxed DNA coiling and increases transcription - ANSWER-DNA Acetylation Removal of acetyl group, tightens DNA coiling and decreases transcription - ANSWER-Histone deacetylation NucleoSide - ANSWER-Base + sugar NucleoTide - ANSWER-Base + phosphate PURines (A.G)- 2 rings - ANSWER-PURe As Gold PYrimidines (C,U,T) - 1 ring - ANSWER-CUT the PY Deamination reaction Cytosine - Uracil - ANSWER-2 H bonds. Increase C-G content, increases melting temperature of DNA. C-G bonds are like "crazy glue" Deamination of adenine makes - ANSWER-hypoxanthine Deamination of guanine forms - ANSWER-Xanthine Deamination of 5-methylcytosine - ANSWER-Thymine Uracil found in? - ANSWER-RNA Thymine found in? - ANSWER-DNA methylation of uracil makes - ANSWER-Thymine Amino acids necessary for purine synthesis? - ANSWER-Cats "purr" until the GAG Glycine Aspartate Glutamine *Pyrimidine synthesis* Leflunomide does what? - ANSWER-inhibits dihydroorotate dehydrogenase *Pyrimidine synthesis* 5-fluorouracil (5-FU) and its prodrug Capecitabine does what? (Drug) - ANSWER-Forms 5-F-dUMP, which inhibits thymidylate synthase (decreases dTMP) *Purine synthesis* 6-mercaptopurine (6-MP) and prodrug Azathioprine does what? (Drug) - ANSWER-inhibit de novo purine synthesis *Purine synthesis* Mycophenolate and Ribavirin does what? (Drug) - ANSWER-inhibit inosine monophosphate dehydrogenase *Purine and pyrimidine synthesis* Hydroxyurea (drug) does what? - ANSWER-Inhibits ribonucleotide reductase *Purine and pyrimidine synthesis* Methotrexate (MTX), trimethoprim (TMP), pyrimethamine (drugs) does what? - ANSWER-inhibits dihydrofolate reductase ( decreases deoxythymidine monophosphate (dTMP) in humans, bacteria, and protozoa. CPS1 - ANSWER-Mitochondria (urea cycle) CPS2 - ANSWER-Cytosol (cyTWOsol) Required for degradation of adenosine and deoxyadenosine. Decreases ADA and increases dATP. - ANSWER-Adenosine deaminase deficiency Decreases reductase activity - ANSWER-Adenosine deaminase deficiency Causes lymphotoxicity - ANSWER-Adenosine deaminase deficiency Major cause of SCID - ANSWER-Adenosine deaminase deficiency SCID - ANSWER-severe combined immunodeficiency disease Defective purine salvage due to absent HGPRT, which converts hypoxanthine to IMP and guanine to GMP. Results in excess uric acid production and de novo purine synthesis. - ANSWER-Lesch-Nyhan syndrome Lesch-Nyhan syndrome: genetics? - ANSWER-X-linked recessive. HGPRT gene: "H e's G ot P urine R ecovery T rouble" Lesch-Nyhan syndrome: findings? - ANSWER-Retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis. *ORANGE "SAND" (sodium urate) in diaper***** Lesch-Nyhan syndrome: treatment? - ANSWER-allopurinol or febuxostat (2nd line) What does HGPRT stand for? - ANSWER-Hyperuricemia Gout Pissed off (aggression, self-mutilation) DysTonia What does unambiguous mean? - ANSWER-Each codon specifies only 1 amino acid Degenerate/redundant - ANSWER-Most amino acids are coded by multiple codons. Example of degenerate/ redundant genetic code? - ANSWER-'WOBBLE"- codons that differ in 3rd ("wobble") position may code for the same tRNA/ amino acid. Specific base pairing is usually required only in the first 2 nucleotide positions of mRNA codon. Degenerate/ redundant exceptions? - ANSWER-Methionine (AUG) and tryptophan (UGG) encoded by only 1 codon Commaless, nonoverlapping - ANSWER-read from a fixed starting point as a continuous sequence of bases Exceptions: some viruses Universal genetic codes - ANSWER-Genetic code is conserved throughout evolution Exception in humans: Mitochondria DNA replication - ANSWER-More complicated than prokaryotic replication and uses continuous and discontinuous (OKAZAKI fragments) synthesis. Occurs in a 5'-3' direction. replication fork - ANSWER-A Y-shaped region on a replicating DNA molecule where new strands are growing. Helicase - ANSWER-Unwinds DNA at replication fork *Deficient in Bloom syndrome (BLM gene mutation) Bloom Syndrome - ANSWER-AR inheritance of Ch15 causing DNA fragility Feats: - short stature - telangiectatic erythema of the face (improves with age) - AbN facies incl microcephaly, prominent ears, malar hypoplasia, long arms, large hands/feet, acanthosis nigricans, Cafe au lait spots, syndactyly, polydactyly and clinodactyly - Normal IQ - primary hypogonadism Issue is INCREASED CANCER RISK, esp lymphoma, leukaemia, carcinomas and Wilm's tumour Deficient in BLM gene single stranded binding protein - ANSWER-Prevents strands from reannealing Creates a single or double stranded break in the helix to add or remove supercoils - ANSWER-DNA topoisomerase What inhibits topoisomerase (TOP 1) in eukaryotes? - ANSWER-Irinotecan and topotecan What inhibits TOP II? - ANSWER-Etoposide and teniposide What inhibits TOP II (DNA gyrase) and TOP IV in prokaryotes? - ANSWER-Fluoroquinolones What makes RNA primer so DNA polymerase III can initiate replication - ANSWER-Primase Prokaryotes only. Elongates leading strand by adding deoxynucleotides to the 3' end. Elongates lagging strand until it reaches primer of preceding fragment. - ANSWER-DNA polymerase What has 5'-3' synthesis and proofreads with 3'-5' exonuclease - ANSWER-DNA polymerase III True or false: Drugs blocking DNA replication have a modified 3' OH, preventing addition of the next nucleotide? - ANSWER-True Prokaryotes only. Degrades RNA primer; replaces it with DNA - ANSWER-DNA polymerase I same functions as DNA polymerase III, also excises RNA primer with 5'-3' exonuclease - ANSWER-DNA polymerase I What catalyzes the formation of a phosphodiester bond within a strand of double-stranded DNA - ANSWER-DNA ligase What joins Okazaki fragments? - ANSWER-DNA ligase. "Ligase Links DNA" Telomerase - ANSWER-Eukaryotes only. A reverse transcriptase (RNA dependent DNA polymerase) that adds DNA (TTAGGG) to 3' ends of chromosomes to avoid loss of genetic material with every duplication. What is dysregulated in cancer cells, allowing unlimited replication. - ANSWER-Telomerase "Telomerase TAGs for Greatness and Glory Transition mutation - ANSWER-purine to purine (A to G) or pyrimidine to pyrimidine (C to G) Transversion mutation - ANSWER-A point mutation in which a pyrimidine is substituted for a purine (C to G), or vice versa (A to T). silent mutation - ANSWER-Nucleotide substitution codes for same (synonymous) amino acid; often base in 3rd position of codon (tRNA wobble) Missense mutation - ANSWER-A base-pair substitution that results in a codon that codes for a different amino acid. Sickle cell disease is an example of what kind of mutation? - ANSWER-Missense mutation What nucleotide substitution results in early STOP codon. Usually results in nonfunctional protein. - ANSWER-Nonsense mutation What are the STOP codons? - ANSWER-UAA, UAG, UGA frameshift mutation - ANSWER-mutation that shifts the "reading" frame of the genetic message by inserting or deleting a nucleotide. Deletion or insertion of a number of nucleotides not divisible by 3 What kind of mutations are Duchenne muscular dystrophy and Tay-Sachs disease? - ANSWER-Frameshift mutation splice site mutation - ANSWER-mutation at a point where coding and non-coding regions meet in a section of DNA. Retained intron in mRNA, protein with impaired or altered function. what are examples of splice site mutation? - ANSWER-rare causes of cancers, dementia, epilepsy, some types of B-thalassemia, gaucher disease, marfan syndrome Preferred metabolic substrate of E. Coli? - ANSWER-Glucose What happens when the glucose is absent and lactose is available? - ANSWER-The lac operon is activated to switch to lactose metabolism. lac operon - ANSWER-a gene system whose operator gene and three structural genes control lactose metabolism in E. coli What happens with the lac operon with low glucose? - ANSWER-1) increased adenylate, 2) increased cyclase activity, 3) increased generation of cAMP from ATP, 4) activation of catabolite activator protein (CAP) and 5) increased transcription What happens with lac operon with high lactose? - ANSWER-1) unbinds repressor protein from repressor/ operator site and 2) increases transcription DNA repair: single strand nucleotide excision repair - ANSWER-Specific endonucleases release the oligonucleotides containing damaged bases; DAN polymerase and ligase fill and reseal the gap. What repairs bulky helix-distorting lesions? - ANSWER-Nucleotide excision repair what phase does nucleotide excision repair take place? - ANSWER-G1 phase what is defective in xeroderma pigmentosum ? - ANSWER-nucleotide excision repair Xeroderma pigmentosum - ANSWER-Mutated single strand nucleotide excision repair gene, which prevents repair of thymidine dimers.; Dry skin w/ melanoma and other cancers ("children of the night"). Also extreme light sensitivity base excision repair - ANSWER-Base specific glycosylases remove altered base and creates AP site (apurinic/ apyrimidinic). One or more nucleotides are removed by AP endonucleases that cleaves the 5' end, AP-Lyase cleaves the 3' end, and DNA polymerase-B fills gap and ligase seals it. what is important in repair of spontaneous/ toxic deamination? - ANSWER-Base excision repair What does GEL PLease stand for with base excision repair? - ANSWER-Glycosylase Endonuclease Lyase Polymerase-B Ligase mismatch repair - ANSWER-Mismatched nucleotides in newly synthesized (unmethylated) strand are removed and gap is filled and resealed. what phase does mismatch repair take place? - ANSWER-S phase What is defective in Lynch syndrome (hereditary nonpolyposis colorectal cancer (HNPCC)? - ANSWER-Mismatch repair Double strand nonhomologous end joining - ANSWER-Brings together 2 ends of DNA fragments. To repair double-stranded breaks. No requirement for homology, some DNA may be lost. What is defective in ataxia-telangiectasia? - ANSWER-nonhomologous end joining homologous recombination - ANSWER-Requires 2 homologous DNA duplexes. A strand from damaged dsDNA is repaired using a complementary strand from intact homologous dsDNA as a template. what is defective in breast/ ovarian cancer with BRCA1 mutation and fanconi anemia? - ANSWER-Homologous recombination what is a promoter in gene expression? - ANSWER-Site where RNA polymerase II and multiple other transcription factors bind to DNA upstream from gene locus. (AT-rich upstream sequence with TATA and CAAT boxes) What does the promoted mutation result in? - ANSWER-Dramatic decrease in level of gene transcription What is an enhancer in gene expression? - ANSWER-DNA locus where regulatory proteins "activators" bind, increasing expression of a gene on the same chromosome. What is a silencer in gene expression? - ANSWER-DNA locus where regulatory proteins "repressors" bind, decreasing expression of a gene on the same chromosome RNA polymerases in eukaryotes - ANSWER-I = rRNA II = mRNA (inhibited by alpha-amanitin) III = tRNA RNA polymerase 1 - ANSWER-Makes rRNA, most common present only in nucleolus RNA polymerase II - ANSWER-transcribes mRNA (massive), MicroRNA (miRNA), and nuclear RNA (snRNA) RNA polymerase III - ANSWER-Makes 5S rRNA, tRNA (tiny) Does RNA polymerase III in eukaryotes have proofreading functions? - ANSWER-NO Where does RNA polymerase II open DNA at? - ANSWER-Promoter site RNA polymerase in Prokaryotes - ANSWER-1 RNA polymerase (multisubunit complex) makes all 3 kinds of RNA Where is a-amanitin found and what does it do? - ANSWER-It is found in the Amanita phalloides (death cap mushroom), and it inhibits RNA polymerase II, causes severe hepatotoxicity if ingested. What is Actinomycin also called and what does it do? - ANSWER-Also called Dactinomycin, and inhibits RNA polymerase in both prokaryotes and eukaryotes What does Rifampin do? - ANSWER-inhibits RNA polymerase in prokaryotes Splicing of pre-mRNA - ANSWER-Precursor where mRNA (pre-mRNA) is transformed into mature mRNA. What can alterations in snRNP assembly cause? - ANSWER-Spinal muscular atrophy. snRNP assembly is affected due to decreased SMN protein, causing congenital degeneration of anterior horns of spinal cord, and symmetric weakness (hypotonia "floppy baby syndrome") Introns vs. exons - ANSWER-Exons contain the actual genetic information coding for protein. Introns are intervening noncoding segments of DNA. ("IN trons stay IN the nucleus, whereas EX ons EX it and are EX pressed") tRNA structure - ANSWER-75-90 nucleotides, secondary structure, cloverleaf form, anticodon end is opposite 3' aminoacyl end. All tRNAs, both eukaryotic and prokaryotic, have CCA at 3' end along w/ a high percentage of chemically modified bases. The AA is covalently bound to the 3' end of tRNA. tRNA structure all have what at the end of them? - ANSWER-CCA at 3' end "can carry amino acids"