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{Grippon:2011:nar/gkq913,
author = {Grippon, S and Zhao, Q and Robinson, T and Marshall, JJT and O'Neill, RJ and Manning, H and Kennedy, G and Dunsby, C and Neil, M and Halford, SE and French, PMW and Baldwin, GS},
doi = {nar/gkq913},
journal = {Nucleic Acids Research},
pages = {2593--2603},
title = {Differential modes of DNA binding by mismatch uracil DNA glycosylase from Escherichia coli: implications for abasic lesion processing and enzyme communication in the base excision repair pathway},
url = {http://dx.doi.org/10.1093/nar/gkq913},
volume = {39},
year = {2011}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Mismatch uracil DNA glycosylase (Mug) fromEscherichia coli is an initiating enzyme in thebase-excision repair pathway. As with other DNAglycosylases, the abasic product is potentiallymore harmful than the initial lesion. Since Mug isknown to bind its product tightly, inhibitingenzyme turnover, understanding how Mug bindsDNA is of significance when considering how Muginteracts with downstream enzymes in the baseexcisionrepair pathway. We have demonstrateddifferential binding modes of Mug between its substrateand abasic DNA product using both band shiftand fluorescence anisotropy assays. Mug binds itsproduct cooperatively, and a stoichiometric analysisof DNA binding, catalytic activity and saltdependenceindicates that dimer formation is offunctional significance in both catalytic activity andproduct binding. This is the first report ofcooperativity in the uracil DNA glycosylase superfamilyof enzymes, and forms the basis of productinhibition in Mug. It therefore provides a new perspectiveon abasic site protection and the findingsare discussed in the context of downstream lesionprocessing and enzyme communication in the baseexcision repair pathway.
AU - Grippon,S
AU - Zhao,Q
AU - Robinson,T
AU - Marshall,JJT
AU - O'Neill,RJ
AU - Manning,H
AU - Kennedy,G
AU - Dunsby,C
AU - Neil,M
AU - Halford,SE
AU - French,PMW
AU - Baldwin,GS
DO - nar/gkq913
EP - 2603
PY - 2011///
SN - 1362-4962
SP - 2593
TI - Differential modes of DNA binding by mismatch uracil DNA glycosylase from Escherichia coli: implications for abasic lesion processing and enzyme communication in the base excision repair pathway
T2 - Nucleic Acids Research
UR - http://dx.doi.org/10.1093/nar/gkq913
UR - http://hdl.handle.net/10044/1/26426
VL - 39
ER -