Reference: Ii T, et al. (2007) The yeast Slx5-Slx8 DNA integrity complex displays ubiquitin ligase activity. Cell Cycle 6(22):2800-9

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Abstract


Genetic studies in budding yeast have previously implicated SLX5 and SLX8 in the control of genome stability and sumoylation. These genes encode RING-finger domain proteins that form a complex of unknown function. Because RING-finger proteins comprise a large class of ubiquitin (Ub) ligases, Slx5 and Slx8 were tested for this activity. Here we show that the Slx5-Slx8 complex, but not its individual subunits, stimulates several human and yeast Ub conjugating enzymes, including Ubc1, 4, 5, and Ubc13-Mms2. The RING-finger domains of both subunits are genetically required for suppression of slx sgs1Delta synthetic-lethality, and point mutations that abolish Ub ligase activity in vitro also eliminate in vivo complementation. Targets of the in vitro ubiquitination reaction include the Slx5 and Slx8 subunits themselves, and the homologous recombination proteins Rad52 and Rad57. We propose that the Slx5-Slx8 complex functions as a two-component Ub ligase in vivo and that it controls genome stability and sumoylation via ubiquitination.

Reference Type
Comparative Study | Journal Article | Research Support, N.I.H., Extramural
Authors
Ii T, Fung J, Mullen JR, Brill SJ
Primary Lit For
SLX5 | SLX8 | Slx5-Slx8 SUMO-targeted ubiquitin ligase (STUbL) complex
Additional Lit For
MMS2 | CDC34 | UBC5 | UBC13 | RAD57 | UBC1 | RAD52 | slx5-6 | slx5-8 | slx5-9 | slx8-1 | ... Show all

Gene Ontology Annotations 6 entries for 3 genes


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Gene/ComplexQualifierGene Ontology TermAnnotation ExtensionEvidenceSourceAssigned On
Slx5-Slx8 SUMO-targeted ubiquitin ligase (STUbL) complexenablesubiquitin-protein transferase activityIDAComplexPortal2014-10-16
SLX5contributes toubiquitin-protein transferase activityhas input RAD57IDASGD2019-11-06
SLX5contributes toubiquitin-protein transferase activityhas input RAD52IDASGD2019-11-06
SLX8involved inprotein ubiquitinationIDASGD2013-08-07
SLX8contributes toubiquitin-protein transferase activityhas input RAD57IDASGD2019-11-06
SLX8contributes toubiquitin-protein transferase activityhas input RAD52IDASGD2019-11-06
Showing 1 to 6 of 6 entries

Phenotype Annotations 8 entries for 2 genes


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GenePhenotypeExperiment TypeMutant InformationStrain BackgroundChemicalDetails
SLX5resistance to chemicals: decreased
classical geneticsnull
Allele: slx5-Δ
W303 hydroxyurea
SLX8resistance to chemicals: decreased
classical geneticsnull
Allele: slx8-Δ
W303 hydroxyurea
SLX5resistance to chemicals: decreased
classical geneticsreduction of function
Allele: slx5-6

C494A,C497A mutations in RING domain

W303 hydroxyurea
SLX5resistance to chemicals: decreased
classical geneticsreduction of function
Allele: slx5-8

C556S,H558A,C561S mutations in RING domain

W303 hydroxyurea
SLX5resistance to chemicals: decreased
classical geneticsreduction of function
Allele: slx5-9

deletion of RING domain

W303 hydroxyurea
SLX8resistance to chemicals: decreased
classical geneticsreduction of function
Allele: slx8-6

deletion of RING domain

W303 hydroxyurea
SLX8resistance to chemicals: decreased
classical geneticsreduction of function
Allele: slx8-3

C221S,H223A,C226S mutations in RING domain

W303 hydroxyurea
SLX8resistance to chemicals: decreased
classical geneticsreduction of function
Allele: slx8-1

C221Y mutation in RING domain

W303 hydroxyurea
Showing 1 to 8 of 8 entries

Interaction Annotations


Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions 3 entries for 3 genes

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InteractorInteractorAssayAnnotationActionModification

the slx5-slx8 complex can form ubiquitin chains in vitro

SLX5UBI4Biochemical Activitymanually curatedBait-Hitubiquitinylated lysine

the slx5-slx8 complex can form ubiquitin chains in vitro

SLX8UBI4Biochemical Activitymanually curatedBait-Hitubiquitinylated lysine
SLX8SLX5Reconstituted Complexmanually curatedBait-HitNo Modification
Showing 1 to 3 of 3 entries