ArticleThe Journal of biological chemistry2013
A mathematical model for scanning and catalysis on single-stranded DNA, illustrated with activation-induced deoxycytidine deaminase.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Controllable genome editing with split-engineered base editors.Nature chemical biology · 2021Article
- Role of Dot1L and H3K79 methylation in regulating somatic hypermutation of immunoglobulin genes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Correlations in Somatic Hypermutation Between Sites in IGHV Genes Can Be Explained by Interactions Between AID and/or Polη Hotspots.Frontiers in immunology · 2020Article
- AID-RNA polymerase II transcription-dependent deamination of IgV DNA.Nucleic acids research · 2019Article
- Random Walk Enzymes: Information Theory, Quantum Isomorphism, and Entropy Dispersion.The journal of physical chemistry. A · 2019Article
- The Bayesian optimist's guide to adaptive immune receptor repertoire analysis.Immunological reviews · 2018Review
- Mutations in human AID differentially affect its ability to deaminate cytidine and 5-methylcytidine in ssDNA substrates in vitro.Scientific reports · 2017Article
- Activation-induced deoxycytidine deaminase: Structural basis for favoring WRC hot motif specificities unique among APOBEC family members.DNA repair · 2017Article
- Cytidine deaminase efficiency of the lentiviral viral restriction factor APOBEC3C correlates with dimerization.Nucleic acids research · 2017Article
- A Novel Regulator of Activation-Induced Cytidine Deaminase/APOBECs in Immunity and Cancer: Schrödinger's CATalytic Pocket.Frontiers in immunology · 2017Review
- Functions and Malfunctions of Mammalian DNA-Cytosine Deaminases.Chemical reviews · 2016Review
- Structural analysis of the activation-induced deoxycytidine deaminase required in immunoglobulin diversification.DNA repair · 2016Article
- Better living with hyper-mutation.Environmental and molecular mutagenesis · 2016Review
- Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution.Nature communications · 2015Article
- Random-walk enzymes.Physical review. E, Statistical, nonlinear, and soft matter physics · 2015Article
- Overlapping hotspots in CDRs are critical sites for V region diversification.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Regulation of immunoglobulin class-switch recombination: choreography of noncoding transcription, targeted DNA deamination, and long-range DNA repair.Advances in immunology · 2014Review
- AIDing Chromatin and Transcription-Coupled Orchestration of Immunoglobulin Class-Switch Recombination.Frontiers in immunology · 2014Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We formulated a master equation-based mathematical model to analyze random scanning and catalysis for enzymes that act on single-stranded DNA (ssDNA) substrates. Catalytic efficiencies and intrinsic scanning distances are deduced from the distribution of positions and gap lengths between a series of catalytic events occurring over time, which are detected as point mutations in a lacZα-based reporter sequence containing enzyme target motifs. Mathematical analysis of the model shows how scanning motions become separable from the catalysis when the proper statistical properties of the mutation pattern are used to interpret the readouts. Two-point correlations between all catalytic events determine intrinsic scanning distances, whereas gap statistics between mutations determine their catalytic efficiencies. Applying this model to activation-induced deoxycytidine deaminase (AID), which catalyzes C→U deaminations processively on ssDNA, we have established that deaminations of AGC hot motifs occur at a low rate, ∼0.03 s(-1), and low efficiency, ∼3%. AID performs random bidirectional movements for an average distance of 6.2 motifs, at a rate of about 15 nucleotides per second, and "dwells" at a motif site for 2.7 s while bound >4 min to the same DNA molecule. These results provide new and important insights on how AID may be optimized for generating mutational diversity in Ig genes, and we discuss how the properties of AID acting freely on a "naked" ssDNA relate to the constrained action of AID during transcription-dependent somatic hypermutation and class-switch recombination.
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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.