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AuthorMöhrle, Bettina Mariadc.contributor.author
Date of accession2016-05-31T15:35:39Zdc.date.accessioned
Available in OPARU since2016-05-31T15:35:39Zdc.date.available
Year of creation2016dc.date.created
Date of first publication2016-05-31dc.date.issued
AbstractAccumulation of DNA mutations or impaired DNA damage repair upon aging has been seen as a critical causal contributor to aging of differentiated cells and stem cells and thus ultimately tissues. Experimental evidence though on the role of DNA damage and repair upon aging, however, remains controversial with respect to this paradigm. These data demonstrate an unexpected loss of the DNA damage induced G1-S checkpoint in both young and aged hematopoietic stem and progenitor cells (HSPCs). Induction of chronic double strand breaks via a zinc-finger nuclease further demonstrated that HSPCs strictly avoid accumulation of mutations by undergoing apoptosis rather than repair. Interestingly, aging does not alter the DNA damage response to DSBs in HSPCs and, most importantly, does not result in an elevated DNA mutational load in hematopoiesis in vivo upon repair of DNA damage. These data demonstrate a strong resilience of both the young and the aged hematopoietic system against acquiring DNA mutations in HSPCs in response to DNA damage, indicating an all (perfect repair) or nothing (apoptosis) approach to resolve DNA damage. These data reveal a protective mechanism in both the young and aged hematopoietic system against accumulation of mutations in response to DNA damage.dc.description.abstract
Languageen_USdc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (ohne Print-on-Demand)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_opod_v1dc.rights.uri
KeywordDNA mutationsdc.subject
KeywordZinc finger nucleasedc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHHematopoietic stem cellsdc.subject.mesh
MeSHCell agingdc.subject.mesh
MeSHDNA damagedc.subject.mesh
MeSHCell cycle checkpointsdc.subject.mesh
MeSHZFN4 protein, humandc.subject.mesh
MeSHZinc fingersdc.subject.mesh
TitleStem cell specific mechanisms ensure genomic fidelity within hematopoietic stem cells (HSCs) and upon aging of HSCsdc.title
Resource typeDissertationdc.type
Date of acceptance2016-04-22dcterms.dateAccepted
RefereeGeiger, Hartmutdc.contributor.referee
RefereeKühl, Michaeldc.contributor.referee
DOIhttp://dx.doi.org/10.18725/OPARU-3976dc.identifier.doi
PPN860362469dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-4015-6dc.identifier.urn
GNDZink-Fingerdc.subject.gnd
GNDBlutstammzelledc.subject.gnd
GNDZink-Finger-Proteinedc.subject.gnd
GNDDNS-Schädigungdc.subject.gnd
GNDZellzyklusdc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
InstitutionZentralinstitut für Biomedizinische Technik (ZIBMT)uulm.affiliationSpecific
InstitutionInstitut für Biochemie und Molekulare Biologieuulm.affiliationSpecific
Shelfmark print versionW: W-H 14.698uulm.shelfmark
Grantor of degreeMedizinische Fakultätuulm.thesisGrantor
DCMI TypeTextuulm.typeDCMI
TypeErstveröffentlichunguulm.veroeffentlichung
CategoryPublikationenuulm.category
University Bibliographyjauulm.unibibliographie


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