期刊
ANNUAL REVIEW OF IMMUNOLOGY
卷 26, 期 -, 页码 261-292出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev.immunol.26.021607.090248
关键词
AID; UNG; AP endonuclease; DNA Pol beta; DNA-PK; XRCC4-DNA ligase IV; ATM; Mre11-Nbs1-Rad50; 53BP1; gamma H2AX; germline transcripts; R-loops; end joining
类别
资金
- NIAID NIH HHS [R21 AI062738, R01 AI063026-03, R01 AI63026, R01 AI065639, R21AI62738, R01 AI063026, R01 AI65639, R01AI23283, R01 AI023283, R01 AI023283-23] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI062738, R01AI023283, R01AI063026, R01AI065639] Funding Source: NIH RePORTER
Antibody class switching occurs in mature B cells in response to antigen stimulation and costimulatory signals. It occurs by a unique type of intrachromosomal deletional recombination within special G-rich tandem repeated DNA sequences [called switch, or S, regions located upstream of each of the heavy chain constant (C-H) region genes, except C delta]. The recombination is initiated by the B cell-specific activation-induced cytidine deaminase (AID), which deaminates cytosines in both the donor and acceptor S regions. AID activity converts several dC bases to dU bases in each S region, and the dU bases are then excised by the uracil DNA glycosylase UNG; the resulting a basic sites are nicked by apurinic/apyrimidinic endonuclease (APE). AID attacks both strands of transcriptionally active S regions, but how transcription promotes AID targeting is not entirely clear. Mismatch repair proteins are then involved in converting the resulting single-strand DNA breaks to double-strand breaks with DNA ends appropriate for end-joining recombination. Proteins required for the subsequent S-S recombination include DNA-PK, ATM, Mre11-Rad50-Nbs1, gamma H2AX, 53BP1, Mdc1, and XRCC4-ligase IV. These proteins are important for faithful joining of S regions, and in their absence aberrant recombination and chromosomal translocations involving S regions occur.
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