A DNA double-strand break (DSB) occurs when both sugar-phosphate backbones of a DNA duplex are broken near the same position.

This lesion is fundamentally more difficult to repair than damage confined to one strand. If only one strand is broken or contains a damaged base, the complementary strand can usually remain continuous and provide local sequence information. At a double-strand break, the physical continuity of the chromosome itself is interrupted.

Why an unrepaired break is dangerous

A broken chromosome creates two DNA ends that can be lost, degraded or joined to the wrong partners. Incorrect repair can therefore produce deletions or larger chromosome rearrangements.

Double-strand breaks can arise from ionizing radiation, some chemical reactions, collapse of DNA replication machinery, or deliberate cellular processes that cut DNA as part of recombination.

Two broad repair strategies

Cells use two conceptually different solutions.

Direct end joining

The broken DNA ends can be processed and reconnected directly. This strategy does not require a long homologous DNA template and can therefore operate even when no matching copy is nearby.

Its disadvantage is that damaged or incompatible ends may need to be trimmed or filled before joining, which can change sequence at the repair junction.

Homology-directed repair

Alternatively, the broken DNA can use a highly similar DNA molecule as a template. Sequence complementarity guides alignment and DNA synthesis, allowing missing information to be reconstructed more accurately.

This strategy requires an appropriate homologous template, meaning DNA with closely matching sequence.

Repair outcome depends on available information

The essential tradeoff is therefore informational:

broken ends only
    → rapid direct joining, potentially sequence-altering

broken ends + homologous template
    → sequence-guided reconstruction

The names and detailed proteins differ among organisms, but this distinction is general. The next units treat nonhomologous end joining as the major direct-joining logic and homologous recombination as the template-guided logic.

Double-strand-break repair is consequently not just molecular glue. It is a problem of deciding how much sequence information is available for reconstructing a physically interrupted chromosome.