You have been asked to design a synthetic DNA motif, able to bind transcriptional regulatory proteins. The location on this motif that you will design for protein binding is the  

A.  minor groove of the DNA double helix.
B.  major groove of the DNA double helix.
C.  phosphate backbone of the DNA double helix.
D.  sugar backbone of the DNA double helix.
E.  available hydrogen-bonds of bases in single-stranded DNA.

Clarify Question
· What is the key concept addressed by the question?
· What type of thinking is required?
· What key words does the question contain and what do they mean?

Gather Content
· What do you already know about transcriptional regulatory proteins?

Consider Possibilities
· Consider the different answer options. Which can you rule out?
Choose Answer
· Given what you now know, what information and/or problem solving approach is most likely to produce the correct answer?

Reflect on Process
· Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?


B.  major groove of the DNA double helix.

Clarify Question
· What is the key concept addressed by the question?
        o This question addresses transcriptional regulatory proteins.
· What type of thinking is required?
        o This question is asking you to take what you already know and apply it to this unfamiliar situation.
· What key words does the question contain and what do they mean?
        o Synthetic DNA is an artificially designed and produced piece of DNA.
        o A DNA motif is a specific sequence that is recognizable by DNA-binding proteins.
        o Transcriptional regulatory proteins, also called transcription factors, are proteins that bind DNA to regulate transcription.

Gather Content
· What do you already know about transcriptional regulatory proteins?
        o Transcriptional regulatory proteins are proteins that bind DNA to control when, where, and how much a gene is transcribed.
        o These proteins have special DNA-binding domains, such as the helix-turn-helix or the zinc finger domain.

Consider Possibilities
· Consider the different answer options. Which can you rule out?
        o For a protein to bind a specific DNA motif, can it recognize the phosphate backbone? No, because that will be identical on every piece of DNA.
        o For a protein to bind a specific DNA motif, can it recognize the sugar backbone? No, because that will be identical on every piece of DNA.
        o For a protein to bind a specific DNA motif, can it recognize the open hydrogen bonds of single-stranded DNA? No, because the DNA is double stranded before transcription begins.
Choose Answer
· Given what you now know, what information and/or problem solving approach is most likely to produce the correct answer?
        o So, it makes sense that the regulatory protein is going to need to recognize the unique sequence of bases while the DNA is double-stranded.
        o In fact, regulatory proteins bind DNA in the major groove and not the minor groove, because it gives enough room for the protein to bind along the bases.

Reflect on Process
· Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?
        o This question asked what part of the DNA is use for motif recognition by regulatory proteins.
        o The question required you to take what you already know and apply it to this unfamiliar situation.
        o Did you recognize that regulatory proteins must recognize the unique parts of the DNA – i.e., the sequence of bases?
        o Did you realize that the proteins bind the major groove because the minor groove is not wide enough?

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