Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells.

Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells. Abstract Text:

Jason Morton,M Wayne Davis,Erik M Jorgensen,Dana Carroll,

Zinc-finger nucleases are chimeric proteins consisting of engineered zinc-finger DNA-binding motifs attached to an endonuclease domain. These proteins can induce site-specific DNA double-strand breaks in genomic DNA, which are then substrates for cellular repair mechanisms. Here, we demonstrate that engineered zinc-finger nucleases function effectively in somatic cells of the nematode Caenorhabditis elegans. Although gene-conversion events were indistinguishable from uncut DNA in our assay, nonhomologous end joining resulted in mutations at the target site. A synthetic target on an extrachromosomal array was targeted with a previously characterized nuclease, and an endogenous genomic sequence was targeted with a pair of specifically designed nucleases. In both cases, approximately 20% of the target sites were mutated after induction of the corresponding nucleases. Alterations in the extrachromosomal targets were largely products of end-filling and blunt ligation. By contrast, alterations in the chromosomal target were mostly deletions. We interpret these differences to reflect the abundance of homologous templates present in the extrachromosomal arrays versus the paucity of such templates for repair of chromosomal breaks. In addition, we find evidence for the involvement of error-prone DNA synthesis in both homologous and nonhomologous pathways of repair. DNA ligase IV is required for efficient end joining, particularly of blunt ends. In its absence, a secondary end-joining pathway relies more heavily on microhomologies in producing deletions.

Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells. Publishing Authors By Initials

J Morton,MW Davis,EM Jorgensen,D Carroll,

For similar zinc fingers research abstracts see: zinc fingers research

PUBMED ID PMID:

MEDLINE DATE:

Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 103

Page Numbers: 16370-5

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 23

MONTH: 10

YEAR: 2006

Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells. Keywords Mesh Terms:

KEYWORDS: Zinc Fingers

MESH TERMS: genetics

Chemical & Substance for Abstract: Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells. Information

Substance Name: DNA Ligases

Registry Number: EC 6.5.1.-

Grant and Affiliation Information for Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells.

AFFILIATION: Department of Biochemistry, University of Utah School of Medicine, 15 North Medical Drive East, Salt Lake City, UT 84112, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: T32 GM 07464

ACRONYM: GM

MEDLINETA: Proc Natl Acad Sci U S A

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells Related Publications

• A cognitive behavioral therapy for alcohol-dependent domestic violence offenders: an integrated substance abuse-domestic violence treatment approach (SADV).
• A field investigation of the effects of bovine viral diarrhea virus infection around the time of insemination on the reproductive performance of cattle.
• Acquisition of i.v. cocaine self-administration in adolescent and adult male rats selectively bred for high and low saccharin intake.
• Augmentation of intertransverse process lumbar fusion.
• Birth and a vision: lamaze childbirth education in kenya, East Africa.
• Chronic urinary infections in infants and children.
• Comparing onset of antidepressant action using a repeated measures approach and a traditional assessment schedule.
• Education predicts quality of life among men with prostate cancer cared for in the Department of Veterans Affairs: a longitudinal quality of life analysis from CaPSURE.
• Effect of monensin, energy level, and cow body condition on pregnancy rate in nonlactating beef cows.
• Effects of Exercise Training on Blood Pressure and Renin-Angiotensin System Activation in Overweight Postmenopausal Women in the Dose-Response to Exercise in Women (DREW) Study: 1931: Board #1 May 31 3:30 PM - 5:00 PM.
• Enhanced growth of myelodysplastic colonies in hypoxic conditions.
• Estrogen receptor beta, but not alpha, mediates estrogen's effect on cocaine-induced reinstatement of extinguished cocaine-seeking behavior in ovariectomized female rats.
• Follicular exclusion of autoreactive B cells requires FcgammaRIIb.
• Gadolinium-enhanced off-resonance contrast angiography.
• Health-related quality of life for men with prostate cancer and diabetes: a longitudinal analysis from CaPSURE.
• Impulsivity (delay discounting) for food and cocaine in male and female rats selectively bred for high and low saccharin intake.
• Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells.
• Integrating marriage education into perinatal education.
• Multiinstitutional validation of the UCSF cancer of the prostate risk assessment for prediction of recurrence after radical prostatectomy.
• Multiple initial culture conditions enhance the establishment of cell lines from primary ovarian cancer specimens.
• Natural antibody mediated innate autoimmune response.
• Postnatal development of carotid body glomus cell response to hypoxia.
• Quality of life for men receiving a second treatment for prostate cancer.
• Recovery of balance and gait function 18 months post-spinal shock: a single subject study design: 1648: board #138 may 30 2:00 PM - 3:30 PM.
• Recovery of urinary continence following radical prostatectomy: the impact of prostate volume--analysis of data from the CaPSURE Database.
• Reduced incidence of bony metastasis at initial prostate cancer diagnosis: data from CaPSURE.
• Role of California (Callipepla californica) and Gambel's (Callipepla gambelii) quail in the ecology of mosquito-borne encephalitis viruses in California, USA.
• Social stimuli enhance phencyclidine (PCP) self-administration in rhesus monkeys.
• Temporal expression analysis of the Borrelia burgdorferi paralogous gene family 54 genes BBA64, BBA65, and BBA66 during persistent infection in mice.
• The UBX-regulated network in the haltere imaginal disc of D. melanogaster.