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Article: Cell death caused by single-stranded oligodeoxynucleotide-mediated targeted genomic sequence modification

TitleCell death caused by single-stranded oligodeoxynucleotide-mediated targeted genomic sequence modification
Authors
Issue Date2009
PublisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/ard
Citation
Oligonucleotides, 2009, v. 19 n. 3, p. 281-286 How to Cite?
AbstractTargeted gene repair directed by single-stranded oligodeoxynucleotides (ssODNs) offers a promising tool for biotechnology and gene therapy. However, the methodology is currently limited by its low frequency of repair events, variability, and low viability of "corrected" cells. In this study, we showed that during ssODN-mediated gene repair reaction, a significant population of corrected cells failed to divide, and were much more prone to undergo apoptosis, as marked by processing of caspases and PARP-1. In addition, we found that apoptotic cell death triggered by ssODN-mediated gene repair was largely independent of the ATM/ATR kinase. Furthermore, we examined the potential involvement of the mismatch repair (MMR) proteins in this "correction reaction-induced" cell death. Result showed that while defective MMR greatly enhanced the efficiency of gene correction, compromising the MMR system did not yield any viable corrected clone, indicating that the MMR machinery, although plays a critical role in determining ssODN-directed repair, was not involved in the observed cellular genotoxic responses. © 2009. Mary Ann Liebert, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/124526
ISSN
2013 Impact Factor: 3.077
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong Kong
National Science Foundation
National Basic Research Program of China2004CB518803
HKU CRCG Seed Funding Program
Funding Information:

We thank Prof. Josef Jiricny for the HEK293T-La cell line. We thank Prof. Stefan Zeuzem for LoVo cell line. This work was supported by a joint grant from the Research Grant Council of Hong Kong and the National Science Foundation to J.D.H. and D. L., by National Basic Research Program of China Grant 2004CB518803 to D. L., and by a HKU CRCG Seed Funding Program for Basic Research to J.D.H.

References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Cen_HK
dc.contributor.authorWang, Zen_HK
dc.contributor.authorHuen, MSYen_HK
dc.contributor.authorLu, LYen_HK
dc.contributor.authorLiu, DPen_HK
dc.contributor.authorHuang, JDen_HK
dc.date.accessioned2010-10-31T10:39:23Z-
dc.date.available2010-10-31T10:39:23Z-
dc.date.issued2009en_HK
dc.identifier.citationOligonucleotides, 2009, v. 19 n. 3, p. 281-286en_HK
dc.identifier.issn1545-4576en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124526-
dc.description.abstractTargeted gene repair directed by single-stranded oligodeoxynucleotides (ssODNs) offers a promising tool for biotechnology and gene therapy. However, the methodology is currently limited by its low frequency of repair events, variability, and low viability of "corrected" cells. In this study, we showed that during ssODN-mediated gene repair reaction, a significant population of corrected cells failed to divide, and were much more prone to undergo apoptosis, as marked by processing of caspases and PARP-1. In addition, we found that apoptotic cell death triggered by ssODN-mediated gene repair was largely independent of the ATM/ATR kinase. Furthermore, we examined the potential involvement of the mismatch repair (MMR) proteins in this "correction reaction-induced" cell death. Result showed that while defective MMR greatly enhanced the efficiency of gene correction, compromising the MMR system did not yield any viable corrected clone, indicating that the MMR machinery, although plays a critical role in determining ssODN-directed repair, was not involved in the observed cellular genotoxic responses. © 2009. Mary Ann Liebert, Inc.en_HK
dc.languageengen_HK
dc.publisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/arden_HK
dc.relation.ispartofOligonucleotidesen_HK
dc.rightsThis is a copy of an article published in the Oligonucleotides © 2009 [copyright Mary Ann Liebert, Inc.]; Oligonucleotides is available online at: http://www.liebertonline.com.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAdaptor Proteins, Signal Transducing - drug effects - genetics - metabolism-
dc.subject.meshApoptosis - genetics - physiology-
dc.subject.meshDNA Mismatch Repair - genetics - physiology-
dc.subject.meshDNA, Single-Stranded - genetics - metabolism-
dc.subject.meshGene Targeting-
dc.titleCell death caused by single-stranded oligodeoxynucleotide-mediated targeted genomic sequence modificationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1545-4576&volume=19&issue=3&spage=281&epage=286&date=2009&atitle=Cell+death+caused+by+single-stranded+oligodeoxynucleotides+mediated+targeted+genomic+sequence+modificationen_HK
dc.identifier.emailHuen, MSY:huen.michael@hku.hken_HK
dc.identifier.emailHuang, JD:jdhuang@hkucc.hku.hken_HK
dc.identifier.authorityHuen, MSY=rp01336en_HK
dc.identifier.authorityHuang, JD=rp00451en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1089/oli.2009.0191en_HK
dc.identifier.pmid19653881-
dc.identifier.scopuseid_2-s2.0-70349292572en_HK
dc.identifier.hkuros179175en_HK
dc.identifier.hkuros212501-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70349292572&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume19en_HK
dc.identifier.issue3en_HK
dc.identifier.spage281en_HK
dc.identifier.epage286en_HK
dc.identifier.isiWOS:000270785700008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLiu, C=40261850900en_HK
dc.identifier.scopusauthoridWang, Z=40162656400en_HK
dc.identifier.scopusauthoridHuen, MSY=23004751500en_HK
dc.identifier.scopusauthoridLu, LY=8686996700en_HK
dc.identifier.scopusauthoridLiu, DP=8782684300en_HK
dc.identifier.scopusauthoridHuang, JD=8108660600en_HK

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