Uracil DNA glycosylase activity is dispensable for immunoglobulin class switch - PubMed (original) (raw)
. 2004 Aug 20;305(5687):1160-3.
doi: 10.1126/science.1098444.
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- PMID: 15326357
- DOI: 10.1126/science.1098444
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Uracil DNA glycosylase activity is dispensable for immunoglobulin class switch
Nasim A Begum et al. Science. 2004.
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Abstract
Activation-induced cytidine deaminase (AID) is required for the DNA cleavage step in immunoglobulin class switch recombination (CSR). AID is proposed to deaminate cytosine to generate uracil (U) in either mRNA or DNA. In the second instance, DNA cleavage depends on uracil DNA glycosylase (UNG) for removal of U. Using phosphorylated histone gamma-H2AX focus formation as a marker of DNA cleavage, we found that the UNG inhibitor Ugi did not inhibit DNA cleavage in immunoglobulin heavy chain (IgH) locus during CSR, even though Ugi blocked UNG binding to DNA and strongly inhibited CSR. Strikingly, UNG mutants that had lost the capability of removing U rescued CSR in UNG-/- B cells. These results indicate that UNG is involved in the repair step of CSR yet by an unknown mechanism. The dispensability of U removal in the DNA cleavage step of CSR requires a reconsideration of the model of DNA deamination by AID.
Comment in
- Immunology. UNGstoppable switching.
Unniraman S, Fugmann SD, Schatz DG. Unniraman S, et al. Science. 2004 Aug 20;305(5687):1113-4. doi: 10.1126/science.1102692. Science. 2004. PMID: 15326342 No abstract available. - Comment on "Uracil DNA glycosylase activity is dispensable for immunoglobulin class switch".
Stivers JT. Stivers JT. Science. 2004 Dec 17;306(5704):2042; author reply 2042. doi: 10.1126/science.1105225. Science. 2004. PMID: 15604391 No abstract available.
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