The XPF/MUS81 family belongs to 3'-flap endonuclease that act upon 3'-flap structures and involved in DNA repair pathways that are necessary for the removal of UV-light-induced DNA lesions and cross-links between DNA strands. Family members exist either as heterodimers or as homodimers in their functionally competent states which consist of a catalytic and a noncatalytic subunit. The catalytic subunits have a DX(n)RKX(3)D motif. This motif is required for metal-dependent endonuclease activity but not for DNA junction binding. The equivalent regions of the noncatalytic subunits (ERCC1, EME1, and FAAP24) have diverged. The noncatalytic subunits have roles such as binding ssDNA or an ability to target the endonuclease to defined DNA structures or sites of DNA damage.
Comment:The dsDNA-bound XPF adopts a more compact conformation, which is an activated form of the enzyme.
Comment:The XPF (HhH)2 domain plays a major role in interacting with DNA, the flexibility of the connecting linker sequence between the (HhH)2 and nuclease domain permits the domain movement on binding DNA thereby coupling the (HhH)2 domain and the nuclease domain to recognize and cleave DNA.
Comment:The noncatalytic subunits have roles such as binding ssDNA or an ability to target the endonuclease to defined DNA structures or sites of DNA damage.
Structure:4P0P; Homo sapiens Mus81-Eme1 complex binds flap DNA substrates; contacts at 4A. - View structure with Cn3D
Jiyao W et al.(2023). "The conserved domain database in 2023.",