Microhomology-mediated end joining

MMEJ repair is low in G0/G1 phase but is increased during S-phase and G2 phase of the cell cycle. In contrast, NHEJ operates throughout the cell cycle, and homologous recombination (HR) operates only in late S and G2. ==Double strand break repair pathway choice==

The choice of which pathway is used for double strand break repair is complex. In most cases, MMEJ accounts for a minor proportion (10%) of double strand break repair, most likely in cases where the double strand break is resected but a sister chromatid is not available for homologous recombination. ==Genes required==

A biochemical assay system shows that at least 6 genes are required for microhomology-mediated end joining: FEN1, Ligase III, MRE11, NBS1, PARP1 and XRCC1. All six of these genes are up-regulated in one or more cancers. In humans, DNA polymerase theta, encoded by the POLQ gene, plays a central role in microhomology-mediated end joining. ==In cancer==

Approximately half of all ovarian cancers are deficient in homologous recombination (HR). These HR-deficient tumors upregulate polymerase theta (POLQ), resulting in an increase in MMEJ. These tumors are hyper-reliant upon MMEJ, so that knockdown of polymerase theta results in substantial lethality. In most cell types, MMEJ makes a minor contribution to double strand break repair. The hyper-reliance of HR-deficient tumors upon MMEJ may represent a possible drug target for cancer treatment. MMEJ always involves insertions or deletions, so that it is a mutagenic pathway. Cells with increased MMEJ may have higher genomic instability and a predisposition towards cancer development, although this has not been demonstrated directly. ==In a crustacean==

Penaeus monodon is a marine crustacean widely consumed for its nutritional value. Repair of double-strand breaks in this organism can occur by HRR, but NHEJ is undetectable. While HRR appears to be the major double-strand break repair pathway, MMEJ was also found to play a significant role in repair of DNA double-strand breaks. == References ==

• MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings • DNA double strand break repair in human bladder cancer is error prone and involves microhomology-associated end-joining • Distinctive differences in DNA double-strand break repair between normal urothelial and urothelial carcinoma cells