WBR0541

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Author [[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Genetics
Sub Category SubCategory::General Principles
Prompt [[Prompt::A geneticist is assessing the chromatin structure of a sperm; he intends to isolate the various chromatin components using a novel technique. During the experiment, he notes that DNA is a negatively charged molecular that is bound by positively-charged histones to form an octamer, called a nucleosome. Additionally, he notes that when he eliminates one tripartite structure but maintains the nucleosome, the stability of the DNA stem is compromised with increased susceptibility to nuclease digestion. Which of the following chromatin components is most likely eliminated by the geneticist?]]
Answer A AnswerA::Histone H1
Answer A Explanation AnswerAExp::Histone H1 is outside the nucleosome core. It provides the stability of the DNA stem and prevents the nuclease digestion of the nucleosome.
Answer B AnswerB::Histone H3
Answer B Explanation AnswerBExp::Histone H3 is a component of the nucleosome.
Answer C AnswerC::DNA backbone
Answer C Explanation AnswerCExp::The DNA backbone is a component of the nucleosome.
Answer D AnswerD::ATP
Answer D Explanation AnswerDExp::ATP has no role in the chromatin structure.
Answer E AnswerE::Chromatosome
Answer E Explanation AnswerEExp::Chromatosome is the combination of nucleosome and the linking H1 histones.
Right Answer RightAnswer::A
Explanation [[Explanation::Chromatin is composed of repeated elements that are called nucleosomes. Nucleosomes are composed of DNA molecular bound to a histone tetramer. Core histones of the nucleosome are H2A, H2B, H3, and H4; all of which are tripartite proteins. These histones have a helix-strand-helix motifs on different ends of a long central helix that form a "helix fold". On the other hand, H1 histone, also a tripartite protein, is not located in the core nucleosome. In contrast, it connects 2 nucleosomes and is thus called a "linker histone". The combination of the nucleosome (DNA, H2A, H2B, H3, H4) and H1 linker histone is called a chromatosome. H1 histone and its particular position within the chromatin structure is believed to facilitate the nucleosomal stability and protection from nuclease digestion.

Educational Objective: Histone H1 is a tripartite protein that is called a linker protein because it links 2 nucleosomes to each other without being a part of the core nucleosome itself. Its role is to provide the stability of the DNA stem and to prevent nuclease digestion of the nucleosome. Reference: Arents G, Burlingame RW, Wang BC, Love WE, Moudrianakis EN. The nucleosomal core histone octamer at 3.1 A resolution: a tripartite protein assemble and a left-handed superhelix. Proc. Natl. Acad. Sci. USA 1991; 88:10148-10152

Whitlock JP, Simpson RT. Removal of histone H1 exposes a fifty base pair DNA segment between nucleosomes. Biochemistry. 1976; 15:3307-3314.

Harshman SW, Young NL, Parthun MR, Freitas MA. H1 histones: current perspectives and challenges. Nucl. Acids. Res. 2013; Epub ahead of print.
Educational Objective:
References: ]]

Approved Approved::No
Keyword WBRKeyword::histone, WBRKeyword::chromatin, WBRKeyword::chromatosome, WBRKeyword::nucleosome, WBRKeyword::DNA, WBRKeyword::H1, WBRKeyword::linker, WBRKeyword::nuclease, WBRKeyword::digestion
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