Nonhomologous end joining (NHEJ) repairs a DNA double-strand break by reconnecting the broken ends without requiring an extended homologous DNA template.

The pathway solves an immediate structural problem: two chromosome fragments must be converted back into one continuous DNA molecule.

End recognition and protection

Proteins first bind the broken DNA ends and hold them near one another. This protects the ends from uncontrolled degradation and helps prevent them from joining unrelated breaks elsewhere in the genome.

If the two ends are already chemically compatible, they can sometimes be rejoined with little or no sequence change. Often, however, the break leaves damaged or mismatched ends.

End processing can alter sequence

Before ligation, enzymes may remove damaged nucleotides or fill short gaps. DNA ligase then seals the remaining backbone discontinuities.

Because nucleotides can be removed or added during this processing, the repaired junction may contain a small deletion or insertion.

For example:

original:   ABCD|EFGH
break:      ABCD   EFGH
processing: ABC     FGH
joining:    ABCFGH

The chromosome is continuous again, but sequence information has been lost at the junction.

NHEJ trades template independence for sequence uncertainty

NHEJ does not need a second matching DNA molecule. That makes it broadly useful when a homologous template is unavailable.

The cost is that the pathway cannot always know what sequence occupied damaged or missing nucleotides at the broken ends. Direct joining can therefore be accurate when compatible ends are preserved, but it can also be mutagenic when end processing changes sequence.

This contrasts with homologous recombination, which can copy missing information from a related DNA template.

NHEJ is therefore best understood as a continuity-restoration strategy: it prioritizes reconnecting broken chromosome ends and uses whatever local end information remains, rather than reconstructing the break from a long sequence-matched template.