Ciencias Fundamentales Flashcards
A 42-year-old woman with a history of multiple sclerosis and recurrent urinary tract infections comes to the emergency department because of flank pain and fever. Her temperature is 38.8°C (101.8°F). Examination shows left-sided costovertebral angle tenderness. She is admitted to the hospital and started on intravenous vancomycin. Three days later, her symptoms have not improved. Urine culture shows growth of Enterococcus faecalis. Which of the following best describes the most likely mechanism of antibiotic resistance in this patient?
Vancomycin binds to the d-alanine-d-alanine terminus of peptidoglycan precursors, thereby inhibiting cell wall synthesis of gram-positive bacteria (e.g., Enterococci). Acquisition of van genes (e.g., through transposition of plasmid-encoded genes) can result in a change from the d-alanine-d-alanine sequence to a different amino acid sequence, such as d-alanine-d-lactate (vanA and vanB genes), which inhibits binding of vancomycin to peptidoglycan.
A group of microbiological investigators is studying bacterial DNA replication in E. coli colonies. While the cells are actively proliferating, the investigators stop the bacterial cell cycle during S phase and isolate an enzyme involved in DNA replication. An assay of the enzyme’s exonuclease activity determines that it is active on both intact and demethylated thymine nucleotides (uracil). Which of the following enzymes have the investigators most likely isolated?
DNA polymerase I uses intrinsic 5’→3’ exonuclease activity to remove RNA primers added by primase during bacterial DNA replication and to remove damaged DNA before filling the gaps with DNA nucleotides through its 5’→3’ polymerase activity. DNA polymerase I also proofreads added DNA nucleotides with its intrinsic 3’→5’ exonuclease activity.
In eukaryotes, RNA exonuclease activity is performed by RNase H and flap endonuclease-1.
This young patient has a history of extreme sensitivity to light and presents with squamous cell carcinoma, several ocular abnormalities, and multiple hyperpigmented patches that likely represent precancerous lesions. These clinical findings are consistent with ———-, a rare, autosomal-recessive disease in which the ability to repair UV-induced DNA damage is defective.
eroderma pigmentosum
Mutaciotions in excision endonuclease
A 62-year-old woman comes to the physician for evaluation of a mole on her forearm that has increased in size over the last several months. Physical examination shows a 9-mm skin lesion on the right forearm with irregular borders (malignant melanoma). An excisional biopsy is performed, and genetic analysis shows a mutation in the gene that encodes B-Raf. Which of the following cellular events most likely predisposed this patient to developing this skin lesion?
The formation of covalent bonds between adjacent thymine and cytosine bases creates pyrimidine dimers. These DNA lesions are caused by exposure to UV radiation and form bulky helix distortions that interfere with DNA replication.
An investigator is studying DNA repair processes in an experimental animal. The investigator inactivates a gene encoding a protein that physiologically excises (excision endonuclease) nucleotides from damaged, bulky, helix-distorting DNA strands. A patient with a similar defect in this gene is most likely to present with which of the following findings?
Dry skin and increased photosensitivity are characteristic features of xeroderma pigmentosum. UV radiation (both UVA and UVB) leads to the formation of pyrimidine dimers (usually thymine), which are unable to be repaired by defective excision endonucleases.
