The Rad50 hook domain is a critical determinant of Mre11 complex functions

Author: Wiltzius, J.J.W.; Hohl, M.; Fleming, J.C.; Petrini, J.H.J.

Description: The Mre11 complex (in Saccharomyces cerevisiae: Mre11, Rad50 and Xrs2) influences multiple facets of chromosome break metabolism. A conserved feature of the Mre11 complex is a zinc-coordinating motif in Rad50 called the Rad50 hook. We established a diploid yeast strain, rad50(hook), in which Rad50 is encoded in halves, one from each of the two RAD50 alleles, with the residues constituting the hook deleted. In all respects, rad50(hook) phenocopies complete Rad50 deficiency. Replacing the hook domain with a ligand-inducible FKBP dimerization cassette partially mitigated all phenotypes in a ligand-dependent manner. The data indicate that the Rad50 hook is critical for Mre11 complex-dependent DNA repair, telomere maintenance and meiotic double-strand break formation. Sister chromatid cohesion was unaffected by Rad50 deficiency, suggesting that molecular bridging required for recombinational DNA repair is qualitatively distinct from cohesin-mediated sister chromatid cohesion.

Subject headings: Cell Division; DNA, Fungal/genetics/metabolism; DNA-Binding Proteins/chemistry/genetics/metabolism; Endodeoxyribonucleases/metabolism; Exodeoxyribonucleases/metabolism; Ligands; Meiosis/genetics; Mutation/genetics; Phenotype; Protein Binding; Protein Structure, Tertiary; Recombination, Genetic/genetics; Saccharomyces cerevisiae/genetics/metabolism; Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism; Telomere/metabolism

Publication year: 2005

Journal or book title: Nature Structural & Molecular Biology

Volume: 12

Issue: 5

Pages: 403-407

Find the full text : https://www.nature.com/articles/nsmb928

Find more like this one (cited by): https://scholar.google.com/scholar?cites=6631761870372472986&as_sdt=1000005&sciodt=0,16&hl=en

Type: Journal Article

Serial number: 1716