scholarly journals Base Excision Repair Enzymes Protect Abasic Sites in Duplex DNA from Interstrand Cross-Links

Biochemistry ◽  
2015 ◽  
Vol 54 (9) ◽  
pp. 1849-1857 ◽  
Author(s):  
Suzanne J. Admiraal ◽  
Patrick J. O’Brien
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Duplex Dna ◽  
Abasic Sites ◽  
Repair Enzymes ◽  
Interstrand Cross Links ◽  
Cross Links ◽  
Base Excision

Processing of the abasic sites clustered with the benzo[a]pyrene adducts by the base excision repair enzymes

DNA Repair ◽  
2017 ◽  
Vol 50 ◽  
pp. 43-53 ◽  
Author(s):  
Lidia V. Starostenko ◽  
Nadejda I. Rechkunova ◽  
Natalia A. Lebedeva ◽  
Alexander A. Lomzov ◽  
Vladimir V. Koval ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Abasic Sites ◽  
Repair Enzymes ◽  
Base Excision

scholarly journals Structure of a DNA glycosylase that unhooks interstrand cross-links

2017 ◽  
Vol 114 (17) ◽  
pp. 4400-4405 ◽  
Author(s):  
Elwood A. Mullins ◽  
Garrett M. Warren ◽  
Noah P. Bradley ◽  
Brandt F. Eichman
Keyword(s):  
Base Excision Repair ◽  
Pathogenic Bacteria ◽  
Mutational Analysis ◽  
Excision Repair ◽  
Dna Glycosylase ◽  
Dna Glycosylases ◽  
Docking Model ◽  
Interstrand Cross Links ◽  
Cross Links ◽  
Base Excision

DNA glycosylases are important editing enzymes that protect genomic stability by excising chemically modified nucleobases that alter normal DNA metabolism. These enzymes have been known only to initiate base excision repair of small adducts by extrusion from the DNA helix. However, recent reports have described both vertebrate and microbial DNA glycosylases capable of unhooking highly toxic interstrand cross-links (ICLs) and bulky minor groove adducts normally recognized by Fanconi anemia and nucleotide excision repair machinery, although the mechanisms of these activities are unknown. Here we report the crystal structure of Streptomyces sahachiroi AlkZ (previously Orf1), a bacterial DNA glycosylase that protects its host by excising ICLs derived from azinomycin B (AZB), a potent antimicrobial and antitumor genotoxin. AlkZ adopts a unique fold in which three tandem winged helix-turn-helix motifs scaffold a positively charged concave surface perfectly shaped for duplex DNA. Through mutational analysis, we identified two glutamine residues and a β-hairpin within this putative DNA-binding cleft that are essential for catalytic activity. Additionally, we present a molecular docking model for how this active site can unhook either or both sides of an AZB ICL, providing a basis for understanding the mechanisms of base excision repair of ICLs. Given the prevalence of this protein fold in pathogenic bacteria, this work also lays the foundation for an emerging role of DNA repair in bacteria-host pathogenesis.

Recognition and Removal of Oxidized Guanines in Duplex DNA by the Base Excision Repair Enzymes hOGG1, yOGG1, and yOGG2†

Biochemistry ◽  
2003 ◽  
Vol 42 (38) ◽  
pp. 11373-11381 ◽  
Author(s):  
Michael D. Leipold ◽  
Hillary Workman ◽  
James G. Muller ◽  
Cynthia J. Burrows ◽  
Sheila S. David
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Duplex Dna ◽  
Repair Enzymes ◽  
Base Excision

scholarly journals APOBEC3 enzymes mediate efficacy of cisplatin and are epistatic with base excision repair and mismatch repair in platinum response

NAR Cancer ◽  
2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Kayla L Conner ◽  
Asra N Shaik ◽  
Katie A Marshall ◽  
Ashley M Floyd ◽  
Elmira Ekinci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mismatch Repair ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Cytosine Deamination ◽  
Patient Response ◽  
Breast Cancer Outcomes ◽  
Interstrand Cross Links ◽  
Cross Links ◽  
Base Excision

Abstract Identifying the mechanisms mediating cisplatin response is essential for improving patient response. Previous research has identified base excision repair (BER) and mismatch repair (MMR) activity in sensitizing cells to cisplatin. Cisplatin forms DNA adducts including interstrand cross-links (ICLs) that distort the DNA helix, forcing adjacent cytosines to become extrahelical. These extrahelical cytosines provide a substrate for cytosine deaminases. Herein, we show that APOBEC3 (A3) enzymes are capable of deaminating the extrahelical cytosines to uracils and sensitizing breast cancer cells to cisplatin. Knockdown of A3s results in resistance to cisplatin and induction of A3 expression in cells with low A3 expression increases sensitivity to cisplatin. We show that the actions of A3s are epistatic with BER and MMR. We propose that A3-induced cytosine deamination to uracil at cisplatin ICLs results in repair of uracils by BER, which blocks ICL DNA repair and enhances cisplatin efficacy and improves breast cancer outcomes.

scholarly journals A role for the base excision repair enzyme NEIL3 in replication-dependent repair of interstrand DNA cross-links derived from psoralen and abasic sites

DNA Repair ◽  
2017 ◽  
Vol 52 ◽  
pp. 1-11 ◽  
Author(s):  
Zhiyu Yang ◽  
Maryam Imani Nejad ◽  
Jacqueline Gamboa Varela ◽  
Nathan E. Price ◽  
Yinsheng Wang ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Repair Enzyme ◽  
Abasic Sites ◽  
Cross Links ◽  
Base Excision

Oxidative base damage to DNA: specificity of base excision repair enzymes

2000 ◽  
Vol 462 (2-3) ◽  
pp. 121-128 ◽  
Author(s):  
Jean Cadet ◽  
Anne-Gaëlle Bourdat ◽  
Cédric D'Ham ◽  
Victor Duarte ◽  
Didier Gasparutto ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Base Damage ◽  
Repair Enzymes ◽  
Base Excision ◽  
Dna Specificity ◽  
Oxidative Base Damage

scholarly journals Chemical and structural characterization of interstrand cross-links formed between abasic sites and adenine residues in duplex DNA

2015 ◽  
Vol 43 (7) ◽  
pp. 3434-3441 ◽  
Author(s):  
Nathan E. Price ◽  
Michael J. Catalano ◽  
Shuo Liu ◽  
Yinsheng Wang ◽  
Kent S. Gates
Keyword(s):  
Structural Characterization ◽  
Duplex Dna ◽  
Abasic Sites ◽  
Interstrand Cross Links ◽  
Cross Links

Heat-Shock Proteins Associated with Base Excision Repair Enzymes in HeLa Cells

2000 ◽  
Vol 153 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Frances Mendez ◽  
Margarita Sandigursky ◽  
William A. Franklin ◽  
Mark K. Kenny ◽  
Raichal Kureekattil ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Base Excision Repair ◽  
Hela Cells ◽  
Excision Repair ◽  
Repair Enzymes ◽  
Base Excision ◽  
Shock Proteins
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