Genome-wide map of Apn1 binding sites under oxidative stress in Saccharomyces cerevisiae

• Type of Material: Article
• Authors: Lydia P. Morris, Emory University; Andrew B. Conley, Georgia Institute of Technology; Natalya Degtyareva, Emory University; I. King Jordan, Georgia Institute of Technology; Paul Doetsch, Emory University
• Language: English
• Date: 2017-11-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 John Wiley & Sons, Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1002/yea.3247
• Title of Journal or Parent Work: Yeast
• ISSN: 0749-503X
• Volume: 34
• Issue: 11
• Start Page: 447
• End Page: 458
• Grant/Funding Information: KJ was funded by the School of Biology, Georgia Institute of Technology, and the Alfred P. Sloan Research Fellowship in Computational and Evolutionary Molecular Biology BR-4839.; ND was funded by NIEHS Program Project Grant PO1 ES011163.; ABC was funded by the School of Biology, Georgia Institute of Technology.; PD was funded by NCI Cancer Center Support Grant P30 CA138292, NIEHS Program Project Grant PO1 ES011163, and an Emory University Winship Cancer Institute Catalyst Award.; LPM was funded by NIEHS Program Project Grant PO1 ES011163.
• Keywords: Biotechnology & Applied Microbiology; Microbiology; Life Sciences & Biomedicine; PROTEIN EXPRESSION; Biochemistry & Molecular Biology; CHROMOSOMAL INSTABILITY; DNA-DAMAGE; SPONTANEOUS MUTATION; DNA repair; DEOXYRIBONUCLEIC-ACID; DNA damage; STRAND BREAKS; BASE EXCISION-REPAIR; OXYGEN-METABOLISM; Mycology; EXONUCLEASE-III; IN-VIVO; Science & Technology
• Research Categories: Chemistry, Biochemistry; Health Sciences, Oncology; Biology, Molecular

Abstract

Copyright © 2017 John Wiley & Sons, Ltd. The DNA is cells is continuously exposed to reactive oxygen species resulting in toxic and mutagenic DNA damage. Although the repair of oxidative DNA damage occurs primarily through the base excision repair (BER) pathway, the nucleotide excision repair (NER) pathway processes some of the same lesions. In addition, damage tolerance mechanisms, such as recombination and translesion synthesis, enable cells to tolerate oxidative DNA damage, especially when BER and NER capacities are exceeded. Thus, disruption of BER alone or disruption of BER and NER in Saccharomyces cerevisiae leads to increased mutations as well as large-scale genomic rearrangements. Previous studies demonstrated that a particular region of chromosome II is susceptible to chronic oxidative stress-induced chromosomal rearrangements, suggesting the existence of DNA damage and/or DNA repair hotspots. Here we investigated the relationship between oxidative damage and genomic instability utilizing chromatin immunoprecipitation combined with DNA microarray technology to profile DNA repair sites along yeast chromosomes under different oxidative stress conditions. We targeted the major yeast AP endonuclease Apn1 as a representative BER protein. Our results indicate that Apn1 target sequences are enriched for cytosine and guanine nucleotides. We predict that BER protects these sites in the genome because guanines and cytosines are thought to be especially susceptible to oxidative attack, thereby preventing large-scale genome destabilization from chronic accumulation of DNA damage. Information from our studies should provide insight into how regional deployment of oxidative DNA damage management systems along chromosomes protects against large-scale rearrangements.