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The Slx5 paradox

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TitleInfo
Title
The Slx5 paradox
SubTitle
expression of a sumo-targeted ubiquitin ligase generates toxic poly-sumo chains in yeast
Name (type = personal)
NamePart (type = family)
Mendez-Rivera
NamePart (type = given)
Letzibeth
NamePart (type = date)
1990-
DisplayForm
Letzibeth Mendez-Rivera
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Brill
NamePart (type = given)
Steven J.
DisplayForm
Steven J. Brill
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Madura
NamePart (type = given)
Kiran
DisplayForm
Kiran Madura
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Walworth
NamePart (type = given)
Nancy
DisplayForm
Nancy Walworth
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Bunting
NamePart (type = given)
Samuel
DisplayForm
Samuel Bunting
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (encoding = w3cdtf); (qualifier = exact)
2015
DateOther (qualifier = exact); (type = degree)
2015-01
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2015
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Defects in DNA repair are associated with a variety of human diseases, but the pathways that regulate DNA repair are poorly understood. Protein modification by SUMO remains one of the most elusive mechanisms, even though it is known to be important for genome stability. Sgs1, a RecQ DNA helicase in S. cerevisiae, is important for DNA repair, and genetic screens have shown that the heterodimeric Slx5-Slx8 SUMO-targeted Ub ligase (STUbL) is required for cell viability in its absence. Another factor that genetically connects SUMO to DNA repair is the metalloprotease Wss1. The growth of a wss1Δ sgs1Δ double mutant is reduced compared to either single mutant. Taking a candidate-gene over-expression (OE) approach, I made the unexpected finding that SLX5 over-expression is lethal to cells lacking WSS1. Surprisingly, this lethality did not require its partner protein Slx8, which suggested that this was a novel Slx5 activity. Consistent with this lethality, was also observed when STUbLs such as yeast ULS1 or mammalian RNF4 were expressed in these cells. Further, structure-function analysis showed that lethality due to SLX5 OE required only Slx5’s SUMO interaction Motif’s (SIMs), not its RING domain. Kinetic analysis indicated that SLX5 OE slows the growth of wild-type cells. In contrast, SLX5 OE permanently arrests the growth of wss1∆ cells. While investigating the cause of this lethality, I found that expression of Slx5 SIMs resulted in the accumulation of high molecular weight SUMO conjugates in both wild-type and mutant cells. Interestingly, subsequent repression of Slx5 led to a reduction in the levels of induced poly-SUMO chains and this turnover was more rapid in wild-type than in wss1∆ cells. The fact that the accumulation of poly-SUMO chains required the Ubc9 SUMO conjugating enzyme, but not the Ulp1 or Ulp2 isopeptidases, supports the hypothesis that the SIMs actively promote chain synthesis. Finally, I found that over-expression of SUMO counteracts the lethality of SLX5 OE. This suggests that wss1∆ cells may suffer lethal damage due to a shortage of monomeric SUMO.
Subject (authority = RUETD)
Topic
Biochemistry
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_6066
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (ix, 73 p. : ill.)
Note (type = degree)
M.S.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Proteins--Synthesis
Subject (authority = ETD-LCSH)
Topic
DNA repair
Note (type = statement of responsibility)
by Letzibeth Mendez-Rivera
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3H41T47
Genre (authority = ExL-Esploro)
ETD graduate
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Mendez-Rivera
GivenName
Letzibeth
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-12-15 15:04:24
AssociatedEntity
Name
Letzibeth Mendez-Rivera
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-01-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2016-01-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after January 31st, 2016.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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