RUcore: Rutgers University Community Repository
Prdx1 deficiency in mice promotes tissue specific loss of heterozygosity mediated by deficiency in DNA repair and increased oxidative stress
Descriptive
TitleInfo
Title
Prdx1 deficiency in mice promotes tissue specific loss of heterozygosity mediated by deficiency in DNA repair and increased oxidative stress
Name
(type = personal)
NamePart
(type = family)
Rani
NamePart
(type = given)
Vamsi K.
DisplayForm
Vamsi Rani
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Brenneman
NamePart
(type = given)
Mark
DisplayForm
Mark Brenneman
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Tischfield
NamePart
(type = given)
Jay
DisplayForm
Jay Tischfield
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Shao
NamePart
(type = given)
Changshun
DisplayForm
Changshun Shao
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Kong
NamePart
(type = given)
Ah-Ng Tony
DisplayForm
Ah-Ng Tony Kong
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside 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
(qualifier = exact)
2012
DateOther
(qualifier = exact);
(type = degree)
2012-05
CopyrightDate
(qualifier = exact)
2012
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Loss of the H2O2 scavenger protein encoded by the peroxiredoxin 1 (Prdx1) gene in mice leads to elevated intracellular amounts of reactive oxygen species (ROS) and promotes tumorigenesis in several different tissues. Loss of heterozygosity (LOH) mutations can initiate tumorigenesis through loss of tumor suppressor gene function in somatic cells that carry only one functional allele. A connection between the severity of oxidative stress and the frequency of LOH mutations has not been previously established in vivo. Therefore, in this study, we characterized in vivo LOH in ear fibroblasts and splenic T cells of 3-4 month old Prdx1-deficient mice. We found that loss of Prdx1 significantly elevates ROS levels in T cells and fibroblasts, and that basal levels of ROS are higher in fibroblasts than in T cells, probably due to a less robust Prdx1 peroxidase activity in the former. Using Aprt as a LOH reporter, we observed an elevation in LOH mutation frequency in fibroblasts, but not in T cells, of Prdx1-/- mice compared to Prdx1+/+ mice. The majority of the LOH mutations in both cell types were derived from mitotic recombination (MR) events. Interestingly, Mlh1, which is known to suppress MR between divergent sequences, was found to be significantly down-regulated in fibroblasts, but not in T cells, of Prdx1-/- mice. Additionally, there was no compensatory increase in expression of base excision repair (BER) genes in Prdx1-/- fibroblasts. Since these cells had higher amounts of ROS, it suggests that BER activity may be insufficient to manage the increased oxidative DNA damage load. This could lead to increased formation of SSBs and DSBs, which could require repair by recombination. A combination of increased amounts of ROS, down-regulation of Mlh1 and inefficient BER may have contributed to the elevation of MR in fibroblasts of Prdx1-/- mice. Additionally, my findings suggest that helix-distorting lesions may also be increased in Prdx1-/- ear fibroblasts and T cells. Transcription analyses of genes in different DNA repair pathways in the whole spleen tissue with Prdx1 deficiency revealed significant differences in transcription compared to T cells. I conclude that mechanisms through which Prdx1 deficiency promotes tumorigenesis in specific tissues may be distinct.
Subject
(authority = RUETD)
Topic
Microbiology and Molecular Genetics
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_3910
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
viii, 88 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Vamsi K. Rani
Subject
(authority = ETD-LCSH)
Topic
Heterozygosity
Subject
(authority = ETD-LCSH)
Topic
Mice--Genetics
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000065250
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/T3HH6J0T
Genre
(authority = ExL-Esploro)
ETD doctoral
Back to the top
Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Rani
GivenName
Vamsi
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2012-04-11 17:21:14
AssociatedEntity
Name
Vamsi Rani
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.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
Back to the top
Technical
FileSize
(UNIT = bytes)
1082368
OperatingSystem
(VERSION = 5.1)
windows xp
ContentModel
ETD
MimeType
(TYPE = file)
application/pdf
MimeType
(TYPE = container)
application/x-tar
FileSize
(UNIT = bytes)
1085440
Checksum
(METHOD = SHA1)
06602553d034e6f3c32c825c7453415089e09d82
Back to the top
Statistical Profile