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The bloom syndrome protein, BLM, inhibits homologous recombination by disrupting RAD51 nucleoprotein filaments

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TitleInfo
Title
The bloom syndrome protein, BLM, inhibits homologous recombination by disrupting RAD51 nucleoprotein filaments
Name (type = personal)
NamePart (type = family)
Patel
NamePart (type = given)
Dharm S.
NamePart (type = date)
1989-
DisplayForm
Dharm S. Patel
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Bunting
NamePart (type = given)
Samuel F
DisplayForm
Samuel F Bunting
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Brill
NamePart (type = given)
Steven J
DisplayForm
Steven J Brill
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Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Anderson
NamePart (type = given)
Stephen
DisplayForm
Stephen Anderson
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Ganesan
NamePart (type = given)
Shridar
DisplayForm
Shridar Ganesan
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
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2017
DateOther (qualifier = exact); (type = degree)
2017-10
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2017
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
BRCA1-deficient cells exhibit increased genomic instability following DNA damaging treatments due to a defect in the homologous recombination (HR) DNA repair pathway. Here, we show that the Bloom Syndrome Protein, BLM, mediates the genomic instability observed in BRCA1-deficient cells by a mechanism that depends in part on its anti- recombinogenic activity. Ablation of BLM in BRCA1-deficient cells allows the HR repair pathway to be restored, leading to a partial rescue of the genomic instability and replication fork degradation that is present in BRCA1-deficient cells. The stable accumulation of RAD51 at DNA double-strand break sites is inhibited by BLM in BRCA1-deficient B cells. However, DNA end resection is not impacted by single or co- deletion of BRCA1 and BLM. Furthermore, cells co-deficient in BRCA1 and BLM display limited sensitivity to PARP inhibition. The rescue in HR and PARPi sensitivity phenotypes following deletion of BLM is only present in hypomorphic Brca1Δ11/Δ11 cells, and not in the RING domain deficient Brca1Δ2/Δ2 or nullizygous cells. Importantly, the helicase activity of BLM is required for its anti-recombinogenic function. Lastly, we demonstrate that BLM belongs to a class of anti-recombinases that limit the rate of HR. These results demonstrate that the anti-recombinogenic activity of BLM is of potentially great significance for regulating the balance of HR versus other error-prone repair pathways.
Subject (authority = RUETD)
Topic
Biochemistry
Subject (authority = ETD-LCSH)
Topic
DNA repair
Subject (authority = ETD-LCSH)
Topic
BRCA genes
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_8274
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xii, 128 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Dharm S. Patel
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3280BRG
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Patel
GivenName
Dharm
MiddleName
S.
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2017-08-03 17:52:18
AssociatedEntity
Name
Dharm Patel
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
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)
2017-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2018-10-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 31st, 2018.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical

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ETD
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windows xp
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DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2017-08-09T01:46:53
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2017-08-09T01:46:53
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