WBR0331

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Alison Leibowitz)]]
Exam Type	USMLE Step 1
Main Category	Genetics
Sub Category	General Principles
Prompt	A geneticist, conducting an experiment using rat cells to study the mechanisms of DNA repair, exposes the cells to high doses of radiation and induces DNA single-strand breaks in the double-stranded DNA. He observes that ATP consumption increases and phosphodiester bonds begin to form. Which of the following enzymes is most likely involved in this process?
Answer A	DNA polymerase I
Answer A Explanation	DNA polymerase I is prokaryotic. It degrades RNA primer to replace it with DNA.
Answer B	Primase
Answer B Explanation	Primase makes RNA primers.
Answer C	Helicase
Answer C Explanation	Helicase unwinds DNA templates at the replication fork.
Answer D	Ligase
Answer D Explanation	DNA ligase catalyzes the formation of phosphodiester bonds within a single-strand of double-stranded DNA.
Answer E	Telomerase
Answer E Explanation	Telomerase adds DNA to the 3' end of chromosomes in order to maintain the replicative integrity.
Right Answer	D
Explanation	DNA ligase is the enzyme responsible for the formation of phosphodiester bonds at single-strands in double-stranded DNA. DNA ligase is important in 2 major steps: First in the discontinuous replication of DNA and joining of Okazaki fragments, and second in the radiation-induced DNA single-stranded breaks and their consequent repair. DNA ligase requires ATP. Its activity increases dramatically in replicating cells, such as cells in liver regeneration. There are 2 DNA ligases: DNA ligase I and DNA ligase II, both of which are present in the nucleus and in the cytoplasm, but less likely in the mitochondria. Educational Objective: DNA ligase is responsible for catalyzing the formation of phosphodiester bonds in discontinuous DNA, the Okazaki fragments, and in radiation-induced single-stranded DNA breaks. References: Soderhall S. DNA ligases during rat liver regeneration. Nature.1976; 260;640-642.
Approved	Yes
Keyword	DNA ligase, helix, replication, repair, single-stranded DNA, Okazaki fragments, phosphodiester bonds, enzymes
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