DNA damage response: ataxia telangiectasia: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Biochemistry · DNA damage response: ataxia telangiectasia

Sample item

A 3-year-old has progressive truncal ataxia, conjunctival telangiectasia and recurrent sinopulmonary infections. Serum alpha-fetoprotein is raised and he is unusually sensitive to ionising radiation. Which gene product is defective?

AMSH2, a mismatch repair proteinBATM, a protein kinase that senses double-strand DNA breaksCFrataxin, a mitochondrial iron chaperoneDXPD, a helicase of nucleotide excision repair

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

B. ATM, a protein kinase that senses double-strand DNA breaks

ATM is activated by double-strand breaks and phosphorylates p53, CHK2 and BRCA1 to arrest the cell cycle and coordinate repair. Loss in ataxia telangiectasia causes radiosensitivity, cerebellar degeneration, immunodeficiency with low IgA and a high risk of lymphoma and leukaemia. Raised AFP is a useful marker.

Option by option

A. MSH2, a mismatch repair protein
MSH2 defects cause Lynch syndrome, which presents with colorectal cancer.
B. ATM, a protein kinase that senses double-strand DNA breaks (correct)
ATM deficiency impairs the double-strand break response and gives radiosensitivity with ataxia and telangiectasia.
C. Frataxin, a mitochondrial iron chaperone
Frataxin deficiency causes Friedreich ataxia from a GAA repeat expansion, without telangiectasia or immunodeficiency.
D. XPD, a helicase of nucleotide excision repair
XPD defects cause xeroderma pigmentosum, with UV sensitivity rather than radiosensitivity and ataxia.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is B, ATM, a protein kinase that senses double-strand DNA breaks. ATM is activated by double-strand breaks and phosphorylates p53, CHK2 and BRCA1 to arrest the cell cycle and coordinate repair.

Why is "MSH2, a mismatch repair protein" not the answer?

MSH2 defects cause Lynch syndrome, which presents with colorectal cancer.

Why is "Frataxin, a mitochondrial iron chaperone" not the answer?

Frataxin deficiency causes Friedreich ataxia from a GAA repeat expansion, without telangiectasia or immunodeficiency.

Why is "XPD, a helicase of nucleotide excision repair" not the answer?

XPD defects cause xeroderma pigmentosum, with UV sensitivity rather than radiosensitivity and ataxia.

What concept does this question test?

It tests DNA damage response: ataxia telangiectasia in Biochemistry. Loss in ataxia telangiectasia causes radiosensitivity, cerebellar degeneration, immunodeficiency with low IgA and a high risk of lymphoma and leukaemia. Raised AFP is a useful marker.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study DNA damage response: ataxia telangiectasia?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.