Microhomology-mediated end joining (MMEJ), also known as alternative nonhomologous end-joining (Alt-NHEJ) is one of the pathways for repairing double-strand breaks in DNA.
As reviewed by McVey and Lee,[1] the foremost distinguishing property of MMEJ is the use of microhomologous sequences during the alignment of broken ends before joining, thereby resulting in deletions flanking the original break.
There are multiple pathways for repairing double strand breaks, mainly non-homologous end joining (NHEJ), homologous recombination (HR), and MMEJ.
NHEJ directly joins both ends of the double strand break and is relatively accurate, although small (usually less than a few nucleotides) insertions or deletions sometimes occur.
Besides microhomology footprints, polymerase theta's mutational signature also consists of (infrequent) templated inserts, which are thought to be the result of aborted template-dependent extension, followed by re-annealing at secondary homologous sequences.
In humans, DNA polymerase theta, encoded by the POLQ gene, plays a central role in microhomology-mediated end joining.
[7] Polymerase theta utilizes its helicase domain to displace replication protein A (RPA) from DNA ends and promote microhomology annealing.