Functions of disordered regions in mammalian early base excision repair proteins |
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Authors: | Muralidhar L Hegde Tapas K Hazra Sankar Mitra |
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Institution: | (1) Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-1079, USA;(2) Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555-1079, USA; |
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Abstract: | Reactive oxygen species, generated endogenously and induced as a toxic response, produce several dozen oxidized or modified
bases and/or single-strand breaks in mammalian and other genomes. These lesions are predominantly repaired via the conserved
base excision repair (BER) pathway. BER is initiated with excision of oxidized or modified bases by DNA glycosylases leading
to formation of abasic (AP) site or strand break at the lesion site. Structural analysis by experimental and modeling approaches
shows the presence of a disordered segment commonly localized at the N- or C-terminus as a characteristic signature of mammalian
DNA glycosylases which is absent in their bacterial prototypes. Recent studies on unstructured regions in DNA metabolizing
proteins have indicated their essential role in interaction with other proteins and target DNA recognition. In this review,
we have discussed the unique presence of disordered segments in human DNA glycosylases, and AP endonuclease involved in the
processing of glycosylase products, and their critical role in regulating repair functions. These disordered segments also
include sites for posttranslational modifications and nuclear localization signal. The teleological basis for their structural
flexibility is discussed. |
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