Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
DNA strand break repair is essential for the prevention of multiple human diseases, particularly those which feature neuropathology. To further understand the pathogenesis of these syndromes, we recently developed animal models in which the DNA single-strand break repair (SSBR) components, XRCC1 and DNA Ligase III (LIG3), were inactivated in the developing nervous system. Although biochemical evidence suggests that inactivation of XRCC1 and LIG3 should share common biological defects, we found profound phenotypic differences between these two models, implying distinct biological roles for XRCC1 and LIG3 during DNA repair. Rather than a key role in nuclear DNA repair, we found LIG3 function was central to mitochondrial DNA maintenance. Instead, our data indicate that DNA Ligase 1 is the main DNA ligase for XRCC1-mediated DNA repair. These studies refine our understanding of DNA SSBR and the etiology of neurological disease.
Ahel,
The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates.
2006, Pubmed
Ahel,
The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates.
2006,
Pubmed Almeida,
A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification.
2007,
Pubmed Barzilai,
The contribution of the DNA damage response to neuronal viability.
2007,
Pubmed Bentley,
DNA ligase I is required for fetal liver erythropoiesis but is not essential for mammalian cell viability.
1996,
Pubmed Bentley,
DNA ligase I null mouse cells show normal DNA repair activity but altered DNA replication and reduced genome stability.
2002,
Pubmed Breslin,
DNA 3'-phosphatase activity is critical for rapid global rates of single-strand break repair following oxidative stress.
2009,
Pubmed
,
Xenbase Caldecott,
XRCC1 and DNA strand break repair.
2003,
Pubmed Caldecott,
An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III.
1994,
Pubmed
,
Xenbase Caldecott,
Characterization of the XRCC1-DNA ligase III complex in vitro and its absence from mutant hamster cells.
1995,
Pubmed
,
Xenbase Caldecott,
Single-strand break repair and genetic disease.
2008,
Pubmed Chan,
DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations.
2009,
Pubmed Chen,
Accumulation of oxidatively generated DNA damage in the brain: a mechanism of neurotoxicity.
2007,
Pubmed Das,
Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria.
2010,
Pubmed
,
Xenbase DiMauro,
Mitochondrial disorders in the nervous system.
2008,
Pubmed El-Khamisy,
TDP1 facilitates repair of ionizing radiation-induced DNA single-strand breaks.
2007,
Pubmed El-Khamisy,
Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1.
2005,
Pubmed
,
Xenbase El-Khamisy,
Synergistic decrease of DNA single-strand break repair rates in mouse neural cells lacking both Tdp1 and aprataxin.
2009,
Pubmed Ellenberger,
Eukaryotic DNA ligases: structural and functional insights.
2008,
Pubmed Gao,
DNA ligase III is critical for mtDNA integrity but not Xrcc1-mediated nuclear DNA repair.
2011,
Pubmed
,
Xenbase Garrido,
Composition and dynamics of human mitochondrial nucleoids.
2003,
Pubmed Gredilla,
Mitochondrial DNA repair and association with aging--an update.
2010,
Pubmed Katyal,
TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo.
2007,
Pubmed Katyal,
DNA repair deficiency and neurodegeneration.
2007,
Pubmed Katyal,
DNA strand breaks, neurodegeneration and aging in the brain.
2008,
Pubmed Kretzschmar,
Identification of human DNA topoisomerase I as a cofactor for activator-dependent transcription by RNA polymerase II.
1993,
Pubmed Lakshmipathy,
Mitochondrial DNA ligase III function is independent of Xrcc1.
2000,
Pubmed
,
Xenbase Lakshmipathy,
Antisense-mediated decrease in DNA ligase III expression results in reduced mitochondrial DNA integrity.
2001,
Pubmed
,
Xenbase Lakshmipathy,
The human DNA ligase III gene encodes nuclear and mitochondrial proteins.
1999,
Pubmed
,
Xenbase LeDoux,
Mitochondrial DNA repair: a critical player in the response of cells of the CNS to genotoxic insults.
2007,
Pubmed LeDoux,
Repair of mitochondrial DNA after various types of DNA damage in Chinese hamster ovary cells.
1992,
Pubmed Lee,
The genesis of cerebellar interneurons and the prevention of neural DNA damage require XRCC1.
2009,
Pubmed Lee,
Responding to DNA double strand breaks in the nervous system.
2007,
Pubmed Lindahl,
Instability and decay of the primary structure of DNA.
1993,
Pubmed Liu,
Removal of oxidative DNA damage via FEN1-dependent long-patch base excision repair in human cell mitochondria.
2008,
Pubmed Liu,
DNA repair in mammalian mitochondria: Much more than we thought?
2010,
Pubmed Lombard,
DNA repair, genome stability, and aging.
2005,
Pubmed Ludwig,
A murine AP-endonuclease gene-targeted deficiency with post-implantation embryonic progression and ionizing radiation sensitivity.
1998,
Pubmed McKinnon,
DNA strand break repair and human genetic disease.
2007,
Pubmed McKinnon,
DNA repair deficiency and neurological disease.
2009,
Pubmed Merino,
DNA topoisomerase I is involved in both repression and activation of transcription.
1993,
Pubmed Montecucco,
DNA ligase I is recruited to sites of DNA replication by an interaction with proliferating cell nuclear antigen: identification of a common targeting mechanism for the assembly of replication factories.
1998,
Pubmed Moreira,
The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.
2001,
Pubmed Mortusewicz,
Differential recruitment of DNA Ligase I and III to DNA repair sites.
2006,
Pubmed
,
Xenbase Moser,
RETRACTED: Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase III alpha in a cell-cycle-specific manner.
2007,
Pubmed
,
Xenbase Nash,
XRCC1 protein interacts with one of two distinct forms of DNA ligase III.
1997,
Pubmed Petrini,
DNA ligase I mediates essential functions in mammalian cells.
1995,
Pubmed
,
Xenbase Pinz,
Efficient repair of abasic sites in DNA by mitochondrial enzymes.
1998,
Pubmed
,
Xenbase Pinz,
Action of mitochondrial DNA polymerase gamma at sites of base loss or oxidative damage.
1995,
Pubmed
,
Xenbase Puebla-Osorio,
Early embryonic lethality due to targeted inactivation of DNA ligase III.
2006,
Pubmed
,
Xenbase Rasouli-Nia,
Stable down-regulation of human polynucleotide kinase enhances spontaneous mutation frequency and sensitizes cells to genotoxic agents.
2004,
Pubmed Reynolds,
Defective DNA ligation during short-patch single-strand break repair in ataxia oculomotor apraxia 1.
2009,
Pubmed Shen,
Mutations in hamster single-strand break repair gene XRCC1 causing defective DNA repair.
1998,
Pubmed Shen,
Mutations in PNKP cause microcephaly, seizures and defects in DNA repair.
2010,
Pubmed Simsek,
Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair.
2011,
Pubmed
,
Xenbase Sleeth,
Exchangeability of mammalian DNA ligases between base excision repair pathways.
2004,
Pubmed Sugo,
Neonatal lethality with abnormal neurogenesis in mice deficient in DNA polymerase beta.
2000,
Pubmed Sykora,
Aprataxin localizes to mitochondria and preserves mitochondrial function.
2011,
Pubmed Takashima,
Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy.
2002,
Pubmed Taylor,
Mitochondrial DNA mutations in human disease.
2005,
Pubmed Tebbs,
Requirement for the Xrcc1 DNA base excision repair gene during early mouse development.
1999,
Pubmed Tomkinson,
Completion of base excision repair by mammalian DNA ligases.
2001,
Pubmed Trifunovic,
Premature ageing in mice expressing defective mitochondrial DNA polymerase.
2004,
Pubmed Wallace,
The pathophysiology of mitochondrial disease as modeled in the mouse.
2009,
Pubmed Weissman,
DNA repair, mitochondria, and neurodegeneration.
2007,
Pubmed Whitehouse,
XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair.
2001,
Pubmed
,
Xenbase Wilson,
Processing of nonconventional DNA strand break ends.
2007,
Pubmed Wilson,
Neurodegeneration: nicked to death.
2007,
Pubmed Wilson,
The mechanics of base excision repair, and its relationship to aging and disease.
2007,
Pubmed Wu,
DNA looping alters local DNA conformation during transcription.
1991,
Pubmed Xanthoudakis,
The redox/DNA repair protein, Ref-1, is essential for early embryonic development in mice.
1996,
Pubmed
