Article: article from journal or magazin.
Identification and characterization of the human mus81-eme1 endonuclease.
Journal of Biological Chemistry
Publication types: Journal Article
The faithful and complete replication of DNA is necessary for the maintenance of genome stability. It is known, however, that replication forks stall at lesions in the DNA template and need to be processed so that replication restart can occur. In fission yeast, the Mus81-Eme1 endonuclease complex (Mus81-Mms4 in Saccharomyces cerevisiae) has been implicated in the processing of aberrant replication intermediates. In this report, we identify the human homolog of the Schizosaccharomyces pombe EME1 gene and have purified the human Mus81-Eme1 heterodimer. We show that Mus81-Eme1 is an endonuclease that exhibits a high specificity for synthetic replication fork structures and 3'-flaps in vitro. The nuclease cleaves Holliday junctions inefficiently ( approximately 75-fold less than flap or fork structures), although cleavage can be increased 6-fold by the presence of homologous sequences previously shown to permit base pair "breathing." We conclude that human Mus81-Eme1 is a flap/fork endonuclease that is likely to play a role in the processing of stalled replication fork intermediates.
Amino Acid Sequence, DNA Replication, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Endonucleases/genetics, Endonucleases/metabolism, Humans, Molecular Sequence Data, Saccharomyces cerevisiae Proteins, Schizosaccharomyces pombe Proteins/genetics, Schizosaccharomyces pombe Proteins/metabolism, Sequence Alignment, Substrate Specificity
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