Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The MUS81 endonuclease complex has been shown to play an important role in the repair of stalled or blocked replication forks and in the processing of meiotic recombination intermediates from yeast to humans. This endonuclease is composed of two subunits, MUS81 and EME1. Surprisingly, unlike other organisms, Arabidopsis (Arabidopsis thaliana) has two EME1 homologs encoded in its genome. AtEME1A and AtEME1B show 63% identity on the protein level. We were able to demonstrate that, after expression in Escherichia coli, each EME1 protein can assemble with the unique AtMUS81 to form a functional endonuclease. Both complexes, AtMUS81-AtEME1A and AtMUS81-AtEME1B, are not only able to cleave 3'-flap structures and nicked Holliday junctions (HJs) but also, with reduced efficiency, intact HJs. While the complexes have the same cleavage patterns with both nicked DNA substrates, slight differences in the processing of intact HJs can be detected. Our results are in line with an involvement of both MUS81-EME1 endonuclease complexes in DNA recombination and repair processes in Arabidopsis.
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PMID:Two distinct MUS81-EME1 complexes from Arabidopsis process Holliday junctions. 1933 4

A substantial number of human tumors (approximately 10%) are telomerase negative, and cells in such tumors have been proposed to maintain telomere length by the alternative lengthening of telomeres (ALT) pathway. Although details of the molecular mechanism of ALT are largely unknown, previous studies have shown that telomere homologous recombination (HR) is implicated in the ALT pathway. MUS81 is a DNA structure-specific recombination endonuclease and functions on aberrant DNA replication and recombination. Recently, we demonstrate that MUS81 plays a key role in the maintenance of telomeres in ALT cells (Zeng, et al. Nature Cell Biology, 2009). The MUS81 endonuclease specifically localizes to ALT-associated promyelocytic leukemia nuclear bodies (APBs) and interacts with telomeres in ALT cells. Depletion of MUS81 leads to reduced telomere recombination resulting in the growth arrest of ALT cells. The endonuclease activity of MUS81, regulated by its binding partner TRF2, is found to be essential for telomere post-replicative recombination. This study provides the first direct evidence that MUS81 specifically functions on ALT recombination-based cell survival. The specific function of MUS81 on the ALT pathway provides a potential powerful diagnostic marker and a therapeutic target for ALT tumors.
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PMID:The MUS81 endonuclease is essential for telomerase negative cell proliferation. 1961 16