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by pairwise interaction with most downstream proteins via the disordered
common interaction interface that is located in one of the polypeptide termini;
(b) essentiality of common interface-mediated interaction for efficient in cell
oxidized base repair is shown by its trans-dominant negative activity; (c) the
DGs could be present in cell as megadalton complexes containing both repair
and noncanonical proteins to direct repair via distinct sub-pathways; (d) the
BER complex enhancement by oxidative stress could involve acetylation and
other covalent modifications of DGs and other BER proteins. Contrary to the
early perception of BER being the simplest among the DNA repair pathways,
it is now clear that many profound questions are still unresolved including:
(1) lesion scanning in chromatinized DNA, (2) repair of oxidized bases in
heterochromatin versus euchromatin, (3) the role of the plethora of proteins
involved in chromatin unfolding and remodeling and the impact of their
posttranslational modifications. Future studies should also focus on a compre-
hensive characterization of the role of noncanonical proteins in the repair of
endogenous versus induced oxidized bases, including chromatin-modifying
enzymes involved in oxidized base repair. Understanding how DNA repair
deficiency occurs and affects cellular functions could provide a rational thera-
peutic basis for ameliorating the genotoxic consequences in neurodegenerative
diseases and for sensitizing cells for cancer therapy by blocking DNA repair.
Acknowledgments
The research in the authors' laboratory has been supported by USPHS grants R01 CA81063
(S. M.), R01 CA53791 (S. M.), P01CA92854 (S. M.), and R01 CA98664 (T. I.). This review with
limited focus is not meant to provide a comprehensive coverage of the literature, and many
appropriate references could not be included for which the authors apologize. We thank Drs.
Tapas K. Hazra (Department of Internal Medicine) and Istvan Boldogh (Department of Microbi-
ology and Immunology) at the University of Texas Medical Branch for careful reading of the
manuscript.
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