Staff View
Role of the mismatch repair gene, Msh6, in suppressing genome instability

Descriptive

TypeOfResource
Text
TitleInfo
Title
Role of the mismatch repair gene, Msh6, in suppressing genome instability
Identifier (type = PMCID)
PMC2476210
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.2/rucore00000001073.Manuscript.000051573
Identifier (type = doi)
doi:10.7282/T3MG7MVT
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Genre (authority = RULIB-FS)
Article, Refereed
Genre (authority = NISO JAV)
Accepted Manuscript (AM)
Subject (authority = LCSH)
Topic
DNA repair
Subject (authority = LCSH)
Topic
Genome dynamics and stability
Subject (authority = LCSH)
Topic
Genetic recombination
Subject (authority = local)
Topic
Loss of heterozygosity
Subject (authority = local)
Topic
Mismatch repair
Subject (authority = local)
Topic
MSH6
Subject (authority = local)
Topic
Mitotic recombination
Subject (authority = local)
Topic
Aprt
Subject (authority = local)
Topic
MutSĪ±
Abstract (type = abstract)
Mismatch repair (MMR) is critical for preserving genomic integrity. Failure of this system can accelerate somatic mutation and increase the risk of developing cancer. MSH6, in complex with MSH2, is the MMR protein that mediates DNA repair through the recognition of 1- and 2-bp mismatches. To evaluate the effects of MSH6 deficiency on genomic stability we compared the frequency of in vivo loss of heterozygosity (LOH) between MSH6-proficient and deficient, 129S2 x C57BL/6 F1 hybrid mice that were heterozygous for our reporter gene Aprt. We recovered mutant cells that had functionally lost APRT protein activity and categorized the spectrum of mutations responsible for the LOH events. We also measured the mutant frequency at the X-linked gene, Hprt, as a second reporter for point mutation. In Msh6-/-Aprt+/- mice, mutation frequency at Aprt was elevated in both T cells and fibroblasts by 2.5-fold and 5.7-fold, respectively, over Msh6+/+Aprt+/- littermate controls. While a modest increase in mitotic recombination (MR) was observed in MSH6-deficient fibroblasts compared to wild type controls, point mutation was the predominant mechanism leading to APRT deficiency in both cell types. Base substitution, consisting of multiple types of transitions, accounted for all of the point mutations identified within the Aprt coding region. We also assessed the role of MSH6 in preventing mutations caused by a common environmental mutagen, ionizing radiation (IR). In Msh6-/-Aprt+/- mice, 4 Gy of X-irradiation induced a significant increase in point mutations at both Aprt and Hprt in T cells, but not in fibroblasts. These findings indicate that MutSĪ± reduces spontaneous and IR-induced mutation in a cell-type dependant manner.
PhysicalDescription
Extent (unit = page(s))
13
InternetMediaType
application/pdf
Note (type = publications)
The publisher's final edited version is available at http://www.sciencedirect.com/science/journal/00275107
Name (type = personal)
NamePart (type = family)
Barrera-Oro
NamePart (type = given)
Julio
Role
RoleTerm (authority = marcrt); (type = text)
author
Affiliation
Genetics, Rutgers University
Name (type = personal)
NamePart (type = family)
Liu
NamePart (type = given)
Tzu-Yang
Role
RoleTerm (authority = marcrt); (type = text)
author
Affiliation
Genetics, Rutgers University
Name (type = personal)
NamePart (type = family)
Gorden
NamePart (type = given)
Erin
Role
RoleTerm (authority = marcrt); (type = text)
author
Affiliation
Genetics, Rutgers University
Name (type = personal)
NamePart (type = family)
Kucherlapati
NamePart (type = given)
Raju
Role
RoleTerm (authority = marcrt); (type = text)
author
Affiliation
Harvard Partners Center for Genetics and Genomics and Harvard Medical School
Name (type = personal)
NamePart (type = family)
Shao
NamePart (type = given)
Changshun
Role
RoleTerm (authority = marcrt); (type = text)
author
Affiliation
Genetics, Rutgers University
Name (type = personal)
NamePart (type = family)
Tischfield
NamePart (type = given)
Jay A.
Role
RoleTerm (authority = marcrt); (type = text)
author
Affiliation
Genetics, Rutgers University
Name (authority = RutgersOrg-Department); (type = corporate)
NamePart
Genetics
Name (authority = RutgersOrg-School); (type = corporate)
NamePart
School of Arts and Sciences (SAS) (New Brunswick)
OriginInfo
DateCreated (encoding = w3cdtf); (keyDate = yes); (qualifier = inferred)
2008
Location
PhysicalLocation (authority = marcorg)
NjNbRU
RelatedItem (type = host)
TitleInfo
Title
Shao, Changshun
Identifier (type = local)
rucore00000001073
Extension
DescriptiveEvent
Type
Citation
DateTime (encoding = w3cdtf)
2008
AssociatedObject
Type
Journal
Relationship
Has part
Name
Mutations Research
Identifier (type = volume and issue)
642(1/2)
Reference (type = digital)
http://www.sciencedirect.com/science/journal/00275107
Detail
74-79
Back to the top

Rights

RightsDeclaration (AUTHORITY = FS); (ID = rulibRdec0004)
Copyright for scholarly resources published in RUcore is retained by the copyright holder. By virtue of its appearance in this open access medium, you are free to use this resource, with proper attribution, in educational and other non-commercial settings. Other uses, such as reproduction or republication, may require the permission of the copyright holder.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
Publication
Status
Published
RightsHolder (ID = CRH-1); (type = corporate)
Name
Elsevier
Role
Copyright holder
Back to the top

Technical

ContentModel
Manuscript
MimeType (TYPE = file)
application/pdf
MimeType (TYPE = container)
application/x-tar
FileSize (UNIT = bytes)
204800
Checksum (METHOD = SHA1)
22c9f36ec70410bae816fb62f7f8e0fb853ad70f
Back to the top
Version 8.3.13
Rutgers University Libraries - Copyright ©2020