Oxidized base damage and single-strand break repair in mammalian genomes: Role of disordered regions and posttranslational modifications in early enzymes

Muralidhar L. Hegde; Tadahide Izumi; Sankar Mitra

doi:10.1016/B978-0-12-387665-2.00006-7

Oxidized base damage and single-strand break repair in mammalian genomes: Role of disordered regions and posttranslational modifications in early enzymes

Muralidhar L. Hegde, Tadahide Izumi, Sankar Mitra

Toxicology and Cancer Biology

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

77 Scopus citations

Abstract

Oxidative genome damage induced by reactive oxygen species includes oxidized bases, abasic (AP) sites, and single-strand breaks, all of which are repaired via the evolutionarily conserved base excision repair/single-strand break repair (BER/SSBR) pathway. BER/SSBR in mammalian cells is complex, with preferred and backup sub-pathways, and is linked to genome replication and transcription. The early BER/SSBR enzymes, namely, DNA glycosylases (DGs) and the end-processing proteins such as abasic endonuclease 1 (APE1), form complexes with downstream repair (and other noncanonical) proteins via pairwise interactions. Furthermore, a unique feature of mammalian early BER/SSBR enzymes is the presence of a disordered terminal extension that is absent in their Escherichia coli prototypes. These nonconserved segments usually contain organelle-targeting signals, common interaction interfaces, and sites of posttranslational modifications that may be involved in regulating their repair function including lesion scanning. Finally, the linkage of BER/SSBR deficiency to cancer, aging, and human neurodegenerative diseases, and therapeutic targeting of BER/SSBR are discussed.

Original language	English
Title of host publication	Progress in Molecular Biology and Translational Science
Pages	123-153
Number of pages	31
DOIs	https://doi.org/10.1016/B978-0-12-387665-2.00006-7
State	Published - 2012

Publication series

Name	Progress in Molecular Biology and Translational Science
Volume	110
ISSN (Print)	1877-1173

Bibliographical note

Funding Information:
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 Microbiology and Immunology) at the University of Texas Medical Branch for careful reading of the manuscript.

Keywords

Base excision repair
DNA glycosylases
Disordered terminal segments
End-processing proteins
Posttranslational modifications
Reactive oxygen species
Repair complexes
Single-strand breaks

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/B978-0-12-387665-2.00006-7

Cite this

Hegde, M. L., Izumi, T., & Mitra, S. (2012). Oxidized base damage and single-strand break repair in mammalian genomes: Role of disordered regions and posttranslational modifications in early enzymes. In Progress in Molecular Biology and Translational Science (pp. 123-153). (Progress in Molecular Biology and Translational Science; Vol. 110). https://doi.org/10.1016/B978-0-12-387665-2.00006-7

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title = "Oxidized base damage and single-strand break repair in mammalian genomes: Role of disordered regions and posttranslational modifications in early enzymes",

abstract = "Oxidative genome damage induced by reactive oxygen species includes oxidized bases, abasic (AP) sites, and single-strand breaks, all of which are repaired via the evolutionarily conserved base excision repair/single-strand break repair (BER/SSBR) pathway. BER/SSBR in mammalian cells is complex, with preferred and backup sub-pathways, and is linked to genome replication and transcription. The early BER/SSBR enzymes, namely, DNA glycosylases (DGs) and the end-processing proteins such as abasic endonuclease 1 (APE1), form complexes with downstream repair (and other noncanonical) proteins via pairwise interactions. Furthermore, a unique feature of mammalian early BER/SSBR enzymes is the presence of a disordered terminal extension that is absent in their Escherichia coli prototypes. These nonconserved segments usually contain organelle-targeting signals, common interaction interfaces, and sites of posttranslational modifications that may be involved in regulating their repair function including lesion scanning. Finally, the linkage of BER/SSBR deficiency to cancer, aging, and human neurodegenerative diseases, and therapeutic targeting of BER/SSBR are discussed.",

keywords = "Base excision repair, DNA glycosylases, Disordered terminal segments, End-processing proteins, Posttranslational modifications, Reactive oxygen species, Repair complexes, Single-strand breaks",

author = "Hegde, {Muralidhar L.} and Tadahide Izumi and Sankar Mitra",

note = "Funding Information: The research in the authors{\textquoteright} 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 Microbiology and Immunology) at the University of Texas Medical Branch for careful reading of the manuscript.",

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Hegde, ML, Izumi, T & Mitra, S 2012, Oxidized base damage and single-strand break repair in mammalian genomes: Role of disordered regions and posttranslational modifications in early enzymes. in Progress in Molecular Biology and Translational Science. Progress in Molecular Biology and Translational Science, vol. 110, pp. 123-153. https://doi.org/10.1016/B978-0-12-387665-2.00006-7

Oxidized base damage and single-strand break repair in mammalian genomes: Role of disordered regions and posttranslational modifications in early enzymes. / Hegde, Muralidhar L.; Izumi, Tadahide; Mitra, Sankar.
Progress in Molecular Biology and Translational Science. 2012. p. 123-153 (Progress in Molecular Biology and Translational Science; Vol. 110).

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

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AU - Hegde, Muralidhar L.

AU - Izumi, Tadahide

AU - Mitra, Sankar

N1 - Funding Information: 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 Microbiology and Immunology) at the University of Texas Medical Branch for careful reading of the manuscript.

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KW - Base excision repair

KW - DNA glycosylases

KW - Disordered terminal segments

KW - End-processing proteins

KW - Posttranslational modifications

KW - Reactive oxygen species

KW - Repair complexes

KW - Single-strand breaks

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ER -

Oxidized base damage and single-strand break repair in mammalian genomes: Role of disordered regions and posttranslational modifications in early enzymes

Abstract

Publication series

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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