Transcription-targeted DNA deamination by the AID antibody diversification enzyme

Jayanta Chaudhuri, Ming Tian, Chan Khuong, Katrin Chua, Eric Pinaud and Frederick W. Alt ()
Additional contact information
Jayanta Chaudhuri: Harvard University Medical School
Ming Tian: Harvard University Medical School
Chan Khuong: Harvard University Medical School
Katrin Chua: Harvard University Medical School
Eric Pinaud: Harvard University Medical School
Frederick W. Alt: Harvard University Medical School

Nature, 2003, vol. 422, issue 6933, 726-730

Abstract: Abstract Activation-induced cytidine deaminase (AID), which is specific to B lymphocytes, is required for class switch recombination (CSR)—a process mediating isotype switching of immunoglobulin—and somatic hypermutation—the introduction of many point mutations into the immunoglobulin variable region genes1,2. It has been suggested that AID may function as an RNA-editing enzyme3 or as a cytidine deaminase on DNA4,5. However, the precise enzymatic activity of AID has not been assessed in previous studies. Similarly, although transcription of the target immunoglobulin locus sequences is required for both CSR and somatic hypermutation, the precise role of transcription has remained speculative6,7,8,9. Here we use two different assays to demonstrate that AID can deaminate specifically cytidines on single-stranded (ss)DNA but not double-stranded (ds)DNA substrates in vitro. However, dsDNA can be deaminated by AID in vitro when the reaction is coupled to transcription. Moreover, a synthetic dsDNA sequence, which targets CSR in vivo in a manner dependent on transcriptional orientation10, was deaminated by AID in vitro with the same transcriptional-orientation-dependence as observed for endogenous CSR. We conclude that transcription targets the DNA deamination activity of AID to dsDNA by generating secondary structures that provide ssDNA substrates.

Date: 2003
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature01574 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:422:y:2003:i:6933:d:10.1038_nature01574

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01574

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().