XPF-like nuclease domain of the family of Essential Meiotic Endonucleases (EMEs) and similar proteins
The family of EMEs includes EME1 and EME2. EME1, also called MMS4 homolog (hMMS4), interacts with MUS81 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Its typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions. EME1 may be required in mitosis for the processing of stalled or collapsed replication forks. EME2 interacts with MUS81 to form a DNA structure-specific endonuclease which cleaves substrates such as 3'-flap structures. MUS81-EME2 is responsible for fork cleavage and restart in human cells. The MUS81-EME2 protein, whose actions are restricted to S phase, is also responsible for telomere maintenance in telomerase-negative ALT (Alternative Lengthening of Telomeres) cells. The nuclease domain of EMEs is a nuclease-like domain which is involved in targeting the MUS81-EME heterodimer complex to DNA. The family also includes budding yeast Mms4 (also known as Eme1 in other organisms), a putative transcriptional (co)activator that protects Saccharomyces cerevisiae cells from endogenous and environmental DNA damage. It interacts with MUS81 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. The nuclease domain of Mms4 lacks the catalytic motif.
Feature 1:nucleic acid substrate binding site [nucleic acid binding site]
Evidence:
Comment:DNA-binding induced conformational changes in the linkers connecting the nuclease and nuclease-like domain of Mus81 and Eme1 facilitating the DNA substrate bending and ultimately place the incision strand at an active site of Mus81.
Structure:4P0P; Homo sapiens Mus81-Eme1 complex binds flap DNA substrates; contacts at 4A.
Jiyao W et al.(2023). "The conserved domain database in 2023.",