Non-homologous end joining: template-free repair of double-strand breaks
Non-homologous end joining (NHEJ) repairs a double-strand break, where both DNA strands are cut, by directly joining the broken ends, with no template (an undamaged DNA copy).
Remember
NHEJ rapidly rejoins the ends of a double-strand break without a template, which makes it fast but error-prone.
Memory aid
A plumber who just clamps two broken pipes together without checking the original plan
Think of NHEJ as a plumber who clamps the two broken ends together without checking a template.
A double-strand break is damage in which both strands of the DNA are cut, which is the most dangerous kind of DNA damage. There is more than one way to repair it, and non-homologous end joining (NHEJ) is the simpler one. The two broken ends are pulled together and glued back, and no undamaged copy of the DNA is needed, which is what "non-homologous" means.
First, the Ku70/80 proteins attach to the exposed ends and cap them to protect them. Next, DNA-PKs (DNA-dependent protein kinases, enzymes that help process the ends and remove damaged DNA if needed) are recruited. Finally, DNA ligase IV seals the two ends back together, working with its partner XRCC4. A ligase is an enzyme that joins DNA, so the name tells you its job. The order to remember is Ku, then DNA-PKs, then ligase IV.
NHEJ is fast and works in all phases of the cell cycle except mitosis, and it is the main route in G1. That phase comes before DNA replication, so no sister chromatid (the copy of the DNA that replication produces) exists yet. Homology-directed repair, by contrast, copies an undamaged template, which is accurate but works mainly in S and G2, the phases in which a sister chromatid is available.
The price is that trimming and joining the ends can lose or add a few bases, so NHEJ is error-prone and may leave small deletions or insertions.
Key facts
- Damage repaired
- double-strand breaks, in which both DNA strands are cut.
- Template
- none is needed; the broken ends are rejoined directly.
- First step
- Ku70/80 bind and cap the broken ends.
- Later steps
- DNA-PKs help process the ends, then DNA ligase IV, with XRCC4, seals them.
- Timing
- active in all cell cycle phases except mitosis, and the main route in G1.
- Accuracy
- error-prone, so small insertions or deletions can be left at the join.
Exam traps
- NHEJ does not repair a damaged base by cutting it out and refilling the gap from the opposite strand, because it joins broken ends; that is base excision repair.
- DNA ligase I does not seal the broken ends in NHEJ, because it acts in DNA replication and base excision repair; DNA ligase IV does the sealing.
- XRCC4 does not itself seal the ends, because it is a partner protein of DNA ligase IV that stabilises the complex.
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