DNA Substrate Length and Surrounding Sequence Affect the Activation-induced Deaminase Activity at Cytidine*
- University of Southern California Norris Comprehensive Cancer Center, Departments of Pathology, Biochemistry & Molecular Biology, Molecular Microbiology & Immunology, and Biological Sciences, Los Angeles, California 90089
- ↵§ To whom correspondence should be addressed. Tel.: 323-865-0568; E-mail: lieber{at}usc.edu.
Abstract
Activation-induced deaminase (AID) is required for both immunoglobulin class switch recombination and somatic hypermutation. AID is known to deaminate cytidines in single-stranded DNA, but the relationship of this step to the class switch or somatic hypermutation processes is not entirely clear. We have studied the activity of a recombinant form of the mouse AID protein that was purified from a baculovirus expression system. We find that the length of the single-stranded DNA target is critical to the action of AID at the Cs positioned anywhere along the length of the DNA. The DNA sequence surrounding a given C influences AID deamination efficiency. AID preferentially deaminates Cs in the WRC motif, and additionally has a small but consistent preference for purine at the position after the WRC, thereby favoring WRCr (the lowercase r corresponds to the smaller impact on activity).
- Received October 23, 2003.
- Revision received November 24, 2003.
- The American Society for Biochemistry and Molecular Biology, Inc.
