microhomologydirected

Microhomology-directed repair, often abbreviated as MMEJ, is a DNA repair pathway that plays a crucial role in fixing double-strand breaks in the genome. Unlike other repair mechanisms such as homologous recombination or non-homologous end joining, MMEJ relies on short stretches of sequence identity, typically between 5 and 25 base pairs, flanking the break site. These microhomologies act as recognition sites for specialized proteins that then bridge the gap and ligate the broken ends.

The process of MMEJ begins with the processing of the double-strand break ends, which often involves some degree of resection to expose single-stranded DNA. These single strands then anneilate to their complementary microhomology sequences on the opposite end of the break. Following annealing, the intervening DNA, which may contain insertions or deletions, is removed, and the gaps are filled in and ligated by DNA polymerases and ligases.

While MMEJ is an important repair pathway, it is often error-prone. The annealing process can sometimes occur at imperfect microhomologies, leading to small insertions or deletions at the repair site. This can have functional consequences, particularly if the repair occurs within a gene, potentially disrupting its coding sequence. MMEJ is thought to be more active in certain cellular contexts, such as when homologous recombination is suppressed or during specific stages of the cell cycle. Its role in genomic stability and its potential contribution to disease, including cancer, are areas of ongoing research.