ArticleProceedings of the National Academy of Sciences of the United States of America1999
The Tyr-265-to-Cys mutator mutant of DNA polymerase beta induces a mutator phenotype in mouse LN12 cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Biochemical, structural and mutational landscapes of base excision repair enzymes and cancer: from atomic resolution to tumor signatures.International journal of radiation biology · 2026Review
- Article
- The hematopoietic compartment is sufficient for lupus development resulting from the POLB-Y265C mutation.PloS one · 2022Article
- DNA glycosylase deficiency leads to decreased severity of lupus in the Polb-Y265C mouse model.DNA repair · 2021Article
- The Pol β variant containing exon α is deficient in DNA polymerase but has full dRP lyase activity.Scientific reports · 2019Article
- I260Q DNA polymerase β highlights precatalytic conformational rearrangements critical for fidelity.Nucleic acids research · 2018Article
- DNA Polymerase β Cancer-Associated Variant I260M Exhibits Nonspecific Selectivity toward the β-γ Bridging Group of the Incoming dNTP.Biochemistry · 2017Article
- A Change in the Rate-Determining Step of Polymerization by the K289M DNA Polymerase β Cancer-Associated Variant.Biochemistry · 2017Article
- Mutation of POLB causes lupus in mice.Cell reports · 2014Article
- Cellular roles of DNA polymerase beta.The Yale journal of biology and medicine · 2013Review
- Y265C DNA polymerase beta knockin mice survive past birth and accumulate base excision repair intermediate substrates.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Base excision repair: contribution to tumorigenesis and target in anticancer treatment paradigms.Current medicinal chemistry · 2012Review
- Genome instability caused by a germline mutation in the human DNA repair gene POLB.PLoS genetics · 2012Article
- Human DNA polymerase beta mutations allowing efficient abasic site bypass.The Journal of biological chemistry · 2011Article
- DNA pol λ's extraordinary ability to stabilize misaligned DNA.Journal of the American Chemical Society · 2010Article
- DNA polymerase family X: function, structure, and cellular roles.Biochimica et biophysica acta · 2010Review
- Article
- The I260Q variant of DNA polymerase beta extends mispaired primer termini due to its increased affinity for deoxynucleotide triphosphate substrates.Biochemistry · 2008Article
- Mismatched and matched dNTP incorporation by DNA polymerase beta proceed via analogous kinetic pathways.Biochemistry · 2008Article
- Loop II of DNA polymerase beta is important for polymerization activity and fidelity.Nucleic acids research · 2007Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
DNA polymerase beta functions in both base excision repair and meiosis. Errors committed by polymerase beta during these processes could result in mutations. Using a complementation system, in which rat DNA polymerase beta substitutes for DNA polymerase I of Escherichia coli, we previously isolated a DNA polymerase beta mutant in which Tyr-265 was altered to Cys (Y265C). The Y265C mutant is dominant to wild-type DNA polymerase beta and possesses an intrinsic mutator activity. We now have expressed the wild-type DNA polymerase and the Y265C mutator mutant in mouse LN12 cells, which have endogenous DNA polymerase beta activity. We demonstrate that expression of the Y265C mutator mutant in the LN12 cells results in an 8-fold increase in the spontaneous mutation frequency of lambdacII mutants compared with expression of the wild-type protein. Expression of Y265C results in at least a 40-fold increase in the frequency of deletions of three bases or more and a 7-fold increase in point mutations. Our results suggest that the mutations we observe in vivo result directly from the action of the mutator polymerase. To our knowledge, this is the first demonstration of a mutator phenotype resulting from expression of a DNA polymerase mutator mutant in mammalian cells. This work raises the possibility that variant polymerases may act in a dominant fashion in human cells, leading to genetic instability and carcinogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.