Evidence map›Paper›PMID 31566237›Full record

ArticleNucleic acids research2019

AID-RNA polymerase II transcription-dependent deamination of IgV DNA.

Phuong Pham, Sohail Malik, Chiho Mak, Peter C Calabrese, Robert G Roeder, Myron F Goodman

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 31 citations in OpenAlex.

  1. De novo rates of aProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. The mechanisms of human lymphoid chromosomal translocations and their medical relevance.Critical reviews in biochemistry and molecular biology · 2022
    Article
  8. Review
  9. Promoter Proximity Defines Mutation Window for VJournal of immunology (Baltimore, Md. : 1950) · 2022
    Article
  10. Article
  11. Article
  12. Article
  13. The role of HIRA-dependent H3.3 deposition and its modifications in the somatic hypermutation of immunoglobulin variable regions.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  14. Article
  15. 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 · 2021
    Article
  16. Article
  17. Article
  18. Review
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Phuong PhamDepartment of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Sohail MalikLaboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
Chiho MakDepartment of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.
Peter C CalabreseDepartment of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Robert G RoederLaboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
Myron F GoodmanDepartment of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
University of Southern California · USRockefeller University · US

Funding

Hypermutation in Bacteria and HumansR35ES028343 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GOODMAN, MYRON · 2017 to 2024
$4.3M
Transcriptional regulatory mechanisms in B cell development and leukemogenesisR01CA178765 · NCI · ROCKEFELLER UNIVERSITY · PI ROEDER, ROBERT G · 2013 to 2017
$2.8M
Biological roles and Mediator-dependent transcription mechanisms of RNA polymerase II(G)R01CA202245 · NCI · ROCKEFELLER UNIVERSITY · PI ROEDER, ROBERT G · 2016 to 2020
$1.9M
NCI NIH HHS R01 CA178765NCI NIH HHS R01 CA202245NIEHS NIH HHS R35 ES028343
6 · The paper itself

Abstract

Activation-induced deoxycytidine deaminase (AID) initiates somatic hypermutation (SHM) in immunoglobulin variable (IgV) genes to produce high-affinity antibodies. SHM requires IgV transcription by RNA polymerase II (Pol II). A eukaryotic transcription system including AID has not been reported previously. Here, we reconstitute AID-catalyzed deamination during Pol II transcription elongation in conjunction with DSIF transcription factor. C→T mutations occur at similar frequencies on non-transcribed strand (NTS) and transcribed strand (TS) DNA. In contrast, bacteriophage T7 Pol generates NTS mutations predominantly. AID-Pol II mutations are strongly favored in WRC and WGCW overlapping hot motifs (W = A or T, R = A or G) on both DNA strands. Single mutations occur on 70% of transcribed DNA clones. Mutations are correlated over a 15 nt distance in multiply mutated clones, suggesting that deaminations are catalyzed processively within a stalled or backtracked transcription bubble. Site-by-site comparisons for biochemical and human memory B-cell mutational spectra in an IGHV3-23*01 target show strongly favored deaminations occurring in the antigen-binding complementarity determining regions (CDR) compared to the framework regions (FW). By exhibiting consistency with B-cell SHM, our in vitro data suggest that biochemically defined reconstituted Pol II transcription systems can be used to investigate how, when and where AID is targeted.

Indexed as

Transcription, GeneticCytidine DeaminaseDeaminationDNADNA-Directed RNA PolymerasesHeLa CellsHumansImmunoglobulin Variable RegionModels, BiologicalMutationNuclear ProteinsRNA Polymerase IISubstrate SpecificityTranscriptional Elongation FactorsViral Proteinsbacteriophage T7 RNA polymeraseCytidine DeaminaseDNADNA-Directed RNA PolymerasesImmunoglobulin Variable RegionNuclear ProteinsRNA Polymerase IISUPT5H protein, humanTranscriptional Elongation FactorsViral Proteins

Identifiers

PMID31566237
PMCPMC6846656
OpenAlexW2978627376

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.