PDBsum entry 2mc3

Hydrolase

PDB id: 2mc3

Contents

Protein chain

103 a.a.

PDB id:

2mc3

Name:

Hydrolase

Title:

Nmr solution structure of the winged-helix domain from mus81 structure-specific endonuclease

Structure:

Mus81 endonuclease homolog (yeast), isoform cra_b. Chain: a. Synonym: cdna flj44872 fis, clone bramy2022320, highly similar to crossover junction endonuclease mus81 (ec 3.1.22.-). Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hcg_23303, mus81. Expressed in: escherichia coli. Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

R.Harris,A.Fadden,N.Q.Mcdonald

Key ref:

A.J.Fadden et al. (2013). A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes. Nucleic Acids Res, 41, 9741-9752. PubMed id: 23982516 DOI: 10.1093/nar/gkt760

Date:

14-Aug-13 Release date: 18-Sep-13

Protein chain

Q96NY9  (MUS81_HUMAN) -  Crossover junction endonuclease MUS81 from Homo sapiens

Seq: 551 a.a.

Struc: 103 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.1.22.- - ?????

DOI no: 10.1093/nar/gkt760

Nucleic Acids Res 41:9741-9752 (2013)

PubMed id: 23982516

A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes.

A.J.Fadden, S.Schalbetter, M.Bowles, R.Harris, J.Lally, A.M.Carr, N.Q.McDonald.

ABSTRACT

The MUS81-EME1 endonuclease maintains metazoan genomic integrity by cleaving branched DNA structures that arise during the resolution of recombination intermediates. In humans, MUS81 also forms a poorly characterized complex with EME2. Here, we identify and determine the structure of a winged helix (WH) domain from human MUS81, which binds DNA. WH domain mutations greatly reduce binding of the isolated domain to DNA and impact on incision activity of MUS81-EME1/EME2 complexes. Deletion of the WH domain reduces the endonuclease activity of both MUS81-EME1 and MUS81-EME2 complexes, and incisions made by MUS81-EME2 are made closer to the junction on substrates containing a downstream duplex, such as fork structures and nicked Holliday junctions. WH domain mutation or deletion in Schizosaccharomyces pombe phenocopies the DNA-damage sensitivity of strains deleted for mus81. Our results indicate an important role for the WH domain in both yeast and human MUS81 complexes.