AID is required to initiate Nbs1/γ-H2AX focus formation and mutations at sites of class switching

Simone Petersen, Rafael Casellas, Bernardo Reina-San-Martin, Hua Tang Chen, Michael J. Difilippantonio, Patrick C. Wilson, Leif Hanitsch, Arkady Celeste, Masamichi Muramatsu, Duane R. Pilch, Christophe Redon, Thomas Ried, William M. Bonner, Tasuku Honjo, Michel C. Nussenzweig and André Nussenzweig ()
Additional contact information
Simone Petersen: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health
Rafael Casellas: Laboratory of Molecular Immunology, The Rockefeller University, and Howard Hughes Medical Institute
Bernardo Reina-San-Martin: Laboratory of Molecular Immunology, The Rockefeller University, and Howard Hughes Medical Institute
Hua Tang Chen: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health
Michael J. Difilippantonio: Genetics Branch, National Cancer Institute, National Institutes of Health
Patrick C. Wilson: Laboratory of Molecular Immunology, The Rockefeller University, and Howard Hughes Medical Institute
Leif Hanitsch: Laboratory of Molecular Immunology, The Rockefeller University, and Howard Hughes Medical Institute
Arkady Celeste: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health
Masamichi Muramatsu: Graduate School of Medicine, Kyoto University
Duane R. Pilch: Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health
Christophe Redon: Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health
Thomas Ried: Genetics Branch, National Cancer Institute, National Institutes of Health
William M. Bonner: Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health
Tasuku Honjo: Graduate School of Medicine, Kyoto University
Michel C. Nussenzweig: Laboratory of Molecular Immunology, The Rockefeller University, and Howard Hughes Medical Institute
André Nussenzweig: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health

Nature, 2001, vol. 414, issue 6864, 660-665

Abstract: Abstract Class switch recombination (CSR) is a region-specific DNA recombination reaction that replaces one immunoglobulin heavy-chain constant region (Ch) gene with another. This enables a single variable (V) region gene to be used in conjunction with different downstream Ch genes, each having a unique biological activity. The molecular mechanisms that mediate CSR have not been defined, but activation-induced cytidine deaminase (AID), a putative RNA-editing enzyme, is required for this reaction1. Here we report that the Nijmegen breakage syndrome protein (Nbs1) and phosphorylated H2A histone family member X (γ-H2AX, also known as γ-H2afx), which facilitate DNA double-strand break (DSB) repair2,3,4, form nuclear foci at the Ch region in the G1 phase of the cell cycle in cells undergoing CSR, and that switching is impaired in H2AX-/- mice. Localization of Nbs1 and γ-H2AX to the Igh locus during CSR is dependent on AID. In addition, AID is required for induction of switch region (Sµ)-specific DNA lesions that precede CSR. These results place AID function upstream of the DNA modifications that initiate CSR.

Date: 2001
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/414660a 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:414:y:2001:i:6864:d:10.1038_414660a

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

DOI: 10.1038/414660a

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 ().