MMS22 like, DNA repair protein (MMS22L)

MMS22L (MMS22 like, DNA repair protein) encodes a DNA repair protein that forms a critical complex with TONSL (tonsoku-like, DNA repair protein), known as the MMS22L-TONSL complex. This complex functions as a genome caretaker and promotes homologous recombination-mediated repair of DNA double-strand breaks and stalled or collapsed replication forks, primarily by facilitating loading and assembly of the RAD51 recombinase on single-stranded DNA. MMS22L is essential for protecting DNA during the replication process and maintaining genome integrity, interacting with RPA-coated ssDNA, RAD51, and potentially NFKBIL2 for chromatin regulation. MMS22L is overexpressed in various cancers, underscoring its importance for rapidly dividing tumor cells and identifying it as a promising target for cancer therapy and chemical sensitization. Loss of MMS22L leads to increased endogenous DNA double-strand breaks and heightened sensitivity to DNA replication stress-inducing agents such as camptothecin. No direct small-molecule inhibitors or approved drugs currently target MMS22L directly; its role is primarily elucidated via genetic depletion or inhibition studies. It is not a receptor, enzyme, ion channel, transporter, or transcription factor, but instead acts as a DNA repair regulator—a chromatin-associated DNA repair facilitator.

Other names

Protein MMS22-likeC6orf167dJ39B17.2Methyl methanesulfonate-sensitivity protein 22-like

Drugs like camptothecin cause replication fork stalling/collapse; MMS22L-TONSL functions to repair these lesions via homologous recombination