1Molecular. Chromatin Structure Nucleotides De novo pyrimidine and purine synthesis Flashcards
A researcher adds DNA to a solution with positively and negatively charged ions. With which of the ions does the DNA precipitate (bind to)?
The positively charged ions (DNA is negatively charged)
How many subunits make up a nucleosome core? What are the subunits?
Eight; two of each of four histone types (H2A, H2B, H3, and H4)
•
A lab researcher induces Barr body (inactive X chromosome) formation. It is transcriptionally inactive. How does this DNA appear on EM?
This is HeteroChromatin, which is Highly Condensed; appears darker and more condensed on EM
What is transcriptionally active DNA called?
Euchromatin—it is uncondensed and accessible to replication enzymes
How many times does DNA loop around each nucleosome core?
Two times
Which nucleotides on the template strand are methylated in DNA replication?
Cytosine and adenine
What is the charge of the histone octamers?
Positive, giving the histones affinity for negatively charged DNA
Methylation at CpG islands ____ (activates/inactivates) transcription of DNA.
Inactivates (CpG Methylation makes DNA Mute)
Predominance of which two amino acids gives histones a positive charge?
Lysine and arginine
Histone ____ (methylation/acetylation) relaxes DNA coiling, allowing transcription.
Acetylation (histone Acetylation makes DNActive)
An experiment is done to tie nucleosome beads together in a string to stabilize chromatin. Which protein facilitates this process?
Histone H1
What allows mismatch repair enzymes to distinguish between old and new DNA strands?
Methylation of the template strand’s cytosine and adenine during DNA replication
How many hydrogen bonds are there between adenine and thymine?
Two
Which two nucleotides are purines?
Adenine and guanine (purines = PURe As Gold
A guanine-cytosine bond is ____ (stronger/weaker) than an adenine-thymine bond.
Guanine-cytosine bond is stronger, as it has three hydrogen bonds—the adenine-thymine bond has only two
What are the three pyrimidines?
Cytosine, Uracil, and Thymine (CUT the PY [pie]: PYrimidines)
What molecule does deamination of cytosine yield?
Uracil
Nucleoside = ____ + (deoxy)ribose
Base
In what type of nucleic acid is uracil found?
• RNA
What type of bond links nucleotides?
3′–5′ phosphodiester bond
In what type of nucleic acid is thymine found?
DNA
What nucleotide has a methyl group?
Thymine (thymine has a methyl)
____ (Nucleotide/nucleoside) = ____ plus (deoxy)ribose
Nucleoside; base
What amino acids are necessary for purine synthesis?
Glycine, Aspartate, Glutamine (GAG)
A novel drug blocks purines, which are ____ and _____. Thus metabolic demand for which amino acids will increase?
Adenosine, guanine. Glycine, Aspartate, and Glutamine (GAG) are needed for purine synthesis, so more of these amino acids are needed
An oncology patient is treated with 5-fluorouracil and methotrexate. Which parts of the pyrimidine synthesis pathway do these inhibit?
Thymidylate synthase and human dihydrofolate reductase (DHFR), respectively, both of which decrease dihydrofolate reductase availability
Trimethoprim (TMP) is a commonly used antibiotic. What mechanism does it target?
Inhibits bacterial dihydrofolate reductase (DHFR)
What enzyme converts the ribonucleotide UDP to the deoxyribonucleotide dUDP?
Ribonucleotide reductase
Deoxyuridine monophosphate (dUMP) is converted to deoxythymidine monophosphate (dTMP) by which enzyme?
Thymidylate synthase
What is the co-factor in the thymidylate synthase reaction (dUMP to dTMP)?
Methylene tetrahydrofolate (methylene THF)
Converting carbamoyl phosphate into orotic acid requires ____ as the cofactor.
Aspartate
Converting phosphoribosyl pyrophosphate (PRPP) into inosinic acid requires ____, ____, ____, and ____.
Aspartate; glycine; glutamine; tetrahydrofolate (THF)
A patient takes 6-mercaptopurine (6-MP) for treatment of her cancer. What is the mechanism of action?
It blocks de novo purine synthesis
What enzyme does hydroxyurea inhibit?
Ribonucleotide reductase
Three pharmacologic treatments decrease deoxythymidine monophosphate (dTMP) through different mechanisms; what are they?
5-fluorouracil (5-FU) blocks dUMP →dTMP; methotrexate (MTX), and trimethoprim (TMP) both block DHF →THF by inhibiting DHFR
What deficiency causes an accumulation of carbamoyl phosphate and, therefore, orotic acid?
Ornithine transcarbamylase deficiency
Dihydrofolic acid (DHF) is converted to tetrahydrofolic acid (THF) by what enzyme?
Dihydrofolate reductase (DHFR
A patient with colon cancer begins chemotherapy that blocks thymidylate synthase. What drug is used? How will it affect dihydrofolate (DHF)?
5-Fluorouracil (FU); inhibits thymidylate synthase, reducing conversion of dUMP to dTMP and N5N10-methylene THF to DHF = less DHF
