DNA Repair and Cancer Quiz

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Which mechanism best describes how non-homologous end joining repairs DNA double-strand breaks?

A Correction of replication mismatches by strand discrimination after DNA synthesis
B Removal of damaged bases followed by DNA synthesis using the complementary strand
C Repair that copies the missing sequence from a sister chromatid during S/G2
D Excision of bulky DNA adducts followed by resynthesis using the intact strand
E Direct joining of the broken DNA ends without using a template ✓

The answer is E: Direct joining of the broken DNA ends without using a template

Explanation

Why E is correct

See Non-homologous end joining. Option E is correct. In a double-strand break both strands of the DNA are cut, which is the most dangerous kind of DNA damage. Non-homologous end joining (NHEJ) repairs it in the simplest way possible: the two broken ends are pulled together and glued back, without copying from a template, which is why it is called non-homologous. The sequence of events is as follows: a pair of proteins called KU70/80 bind to the exposed ends and act like caps that protect them; a protein kinase called DNA-PK then joins them to form a complex that tidies up the ends and removes any damaged DNA; and finally an enzyme called DNA ligase IV (a ligase is an enzyme that joins DNA) seals the ends back together. NHEJ works at every stage of the cell cycle and is fast, but it can lose or add a few bases, so it is less accurate than homology-directed repair. The memory aid is to think of a plumber who just clamps two broken pipes together without checking the original plan.

Double-strand break: both DNA strands are cut.
Non-homologous end joining: the broken ends are joined directly without a template.
Proteins: KU70/80 cap the ends, DNA-PK processes them and DNA ligase IV seals them.
Accuracy: works in every phase but may lose or add a few bases.

Why the other options are incorrect

A. Correction of replication mismatches by strand discrimination after DNA synthesis: Correcting replication mismatches by recognising the new strand describes mismatch repair, which acts after replication on wrongly paired bases. It does not rejoin broken DNA.
B. Removal of damaged bases followed by DNA synthesis using the complementary strand: Removing damaged bases and refilling the gap using the complementary strand describes excision repair of base damage, such as base excision repair. It deals with single-strand lesions rather than double-strand breaks.
C. Repair that copies the missing sequence from a sister chromatid during S/G2: Copying the missing sequence from a sister chromatid in S and G2 phases is homology-directed repair, the other double-strand break pathway. End joining does not copy from a template.
D. Excision of bulky DNA adducts followed by resynthesis using the intact strand: Excising bulky DNA adducts (such as UV-induced dimers) and resynthesising the gap using the intact strand describes nucleotide excision repair. It deals with distorting damage on one strand, not breaks through both.

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1
A researcher is designing a new anti-cancer drug that selectively kills tumour cells while sparing most normal tissues. The drug inhibits a specific DNA repair pathway that is essential only in cancer cells because other repair mechanisms are already defective. Which therapeutic principle best explains this selective tumour cell death?
2
Which feature most directly explains why homology-directed repair is largely restricted to specific phases of the cell cycle?

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