Abstract:
:To initiate class switch recombination (CSR) activation-induced cytidine deaminase (AID) induces staggered nick cleavage in the S region, which lies 5' to each Ig constant region gene and is rich in palindromic sequences. Topoisomerase 1 (Top1) controls the supercoiling of DNA by nicking, rotating, and religating one strand of DNA. Curiously, Top1 reduction or AID overexpression causes the genomic instability. Here, we report that the inactivation of Top1 by its specific inhibitor camptothecin drastically blocked both the S region cleavage and CSR, indicating that Top1 is responsible for the S region cleavage in CSR. Surprisingly, AID expression suppressed Top1 mRNA translation and reduced its protein level. In addition, the decrease in the Top1 protein by RNA-mediated knockdown augmented the AID-dependent S region cleavage, as well as CSR. Furthermore, Top1 reduction altered DNA structure of the Smu region. Taken together, AID-induced Top1 reduction alters S region DNA structure probably to non-B form, on which Top1 can introduce nicks but cannot religate, resulting in S region cleavage.
journal_name
Proc Natl Acad Sci U S Aauthors
Kobayashi M,Aida M,Nagaoka H,Begum NA,Kitawaki Y,Nakata M,Stanlie A,Doi T,Kato L,Okazaki IM,Shinkura R,Muramatsu M,Kinoshita K,Honjo Tdoi
10.1073/pnas.0911879106subject
Has Abstractpub_date
2009-12-29 00:00:00pages
22375-80issue
52eissn
0027-8424issn
1091-6490pii
0911879106journal_volume
106pub_type
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