Imperial College London

DrGeoffBaldwin

Faculty of Natural SciencesDepartment of Life Sciences

Reader in Biochemistry
 
 
 
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Contact

 

+44 (0)20 7594 5288g.baldwin

 
 
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Location

 

508Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Di:2007:10.1084/jem.20071768,
author = {Di, Noia JM and Williams, GT and Chan, DTY and Buerstedde, J-M and Baldwin, GS and Neuberger, MS},
doi = {10.1084/jem.20071768},
journal = {Journal of Experimental Medicine},
pages = {3209--3219},
title = {Dependence of antibody gene diversification on uracil excision},
url = {http://dx.doi.org/10.1084/jem.20071768},
volume = {204},
year = {2007}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Activation-induced deaminase (AID) catalyses deamination of deoxycytidine to deoxyuridinewithin immunoglobulin loci, triggering pathways of antibody diversifi cation that arelargely dependent on uracil-DNA glycosylase (uracil- N -glycolase [UNG]). Surprisinglyeffi cient class switch recombination is restored to ung / B cells through retroviraldelivery of active-site mutants of UNG, stimulating discussion about the need for UNG ’ suracil-excision activity. In this study, however, we fi nd that even with the overexpressionachieved through retroviral delivery, switching is only mediated by UNG mutants thatretain detectable excision activity, with this switching being especially dependent onMSH2. In contrast to their potentiation of switching, low-activity UNGs are relativelyineffective in restoring transversion mutations at C:G pairs during hypermutation, or inrestoring gene conversion in stably transfected DT40 cells. The results indicate that UNGdoes, indeed, act through uracil excision, but suggest that, in the presence of MSH2,effi cient switch recombination requires base excision at only a small proportion of theAID-generated uracils in the S region. Interestingly, enforced expression of thymine-DNAglycosylase (which can excise U from U:G mispairs) does not (unlike enforced UNG orSMUG1 expression) potentiate effi cient switching, which is consistent with a need eitherfor specifi c recruitment of the uracil-excision enzyme or for it to be active on singlestrandedDNA.
AU - Di,Noia JM
AU - Williams,GT
AU - Chan,DTY
AU - Buerstedde,J-M
AU - Baldwin,GS
AU - Neuberger,MS
DO - 10.1084/jem.20071768
EP - 3219
PY - 2007///
SN - 1540-9538
SP - 3209
TI - Dependence of antibody gene diversification on uracil excision
T2 - Journal of Experimental Medicine
UR - http://dx.doi.org/10.1084/jem.20071768
UR - http://hdl.handle.net/10044/1/26425
VL - 204
ER -