↓ Skip to main content

Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression

Overview of attention for article published in Proceedings of the National Academy of Sciences of the United States of America, October 2008
Altmetric Badge

Mentioned by

f1000
1 research highlight platform

Citations

dimensions_citation
94 Dimensions

Readers on

mendeley
83 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression
Published in
Proceedings of the National Academy of Sciences of the United States of America, October 2008
DOI 10.1073/pnas.0808182105
Pubmed ID
Authors

Sergio Roa, Elena Avdievich, Jonathan U. Peled, Thomas MacCarthy, Uwe Werling, Fei Li Kuang, Rui Kan, Chunfang Zhao, Aviv Bergman, Paula E. Cohen, Winfried Edelmann, Matthew D. Scharff

Abstract

Somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes are dependent upon activation-induced cytidine deaminase (AID)-induced mutations. The scaffolding properties of proliferating cell nuclear antigen (PCNA) and ubiquitylation of its residue K164 have been suggested to play an important role organizing the error-prone repair events that contribute to the AID-induced diversification of the Ig locus. We generated knockout mice for PCNA (Pcna(-/-)), which were embryonic lethal. Expression of PCNA with the K164R mutation rescued the lethal phenotype, but the mice (Pcna(-/-)tg(K164R)) displayed a meiotic defect in early pachynema and were sterile. B cells proliferated normally in Pcna(-/-)tg(K164R) mice, but a PCNA-K164R mutation resulted in impaired ex vivo CSR to IgG1 and IgG3, which was associated with reduced mutation frequency at the switch regions and a bias toward blunt junctions. Analysis of the heavy chain V186.2 region after NP-immunization showed in Pcna(-/-)tg(K164R) mice a significant reduction in the mutation frequency of A:T residues in WA motifs preferred by polymerase-eta (Poleta), and a strand-biased increase in the mutation frequency of G residues, preferentially in the context of AID-targeted GYW motifs. The phenotype of Pcna(-/-)tg(K164R) mice supports the idea that ubiquitylation of PCNA participates directly in the meiotic process and the diversification of the Ig locus through class-switch recombination (CSR) and somatic hypermutation (SHM).

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 83 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 2%
United States 2 2%
Vietnam 1 1%
Canada 1 1%
Unknown 77 93%

Demographic breakdown

Readers by professional status Count As %
Researcher 21 25%
Student > Ph. D. Student 19 23%
Student > Master 7 8%
Student > Bachelor 7 8%
Student > Doctoral Student 5 6%
Other 14 17%
Unknown 10 12%
Readers by discipline Count As %
Agricultural and Biological Sciences 37 45%
Biochemistry, Genetics and Molecular Biology 22 27%
Medicine and Dentistry 5 6%
Immunology and Microbiology 3 4%
Philosophy 1 1%
Other 4 5%
Unknown 11 13%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 October 2008.
All research outputs
#16,741,542
of 24,625,114 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#91,769
of 101,438 outputs
Outputs of similar age
#81,062
of 94,954 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#603
of 685 outputs
Altmetric has tracked 24,625,114 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 101,438 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 38.8. This one is in the 5th percentile – i.e., 5% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 94,954 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 8th percentile – i.e., 8% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 685 others from the same source and published within six weeks on either side of this one. This one is in the 2nd percentile – i.e., 2% of its contemporaries scored the same or lower than it.