The role of Schizosaccharomyces pombe DNA repair enzymes Apn1p and Uve1p in the base excision repair of apurinic/apyrimidinic sites

2006 ◽  
Vol 347 (4) ◽  
pp. 889-894 ◽  
Author(s):  
Haruna Tanihigashi ◽  
Ayako Yamada ◽  
Emi Igawa ◽  
Shogo Ikeda
Keyword(s):  
Dna Repair ◽  
Schizosaccharomyces Pombe ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Dna Repair Enzymes ◽  
Repair Enzymes ◽  
Base Excision

scholarly journals New perspectives in cancer biology from a study of canonical and non-canonical functions of base excision repair proteins with a focus on early steps

Mutagenesis ◽  
2019 ◽  
Vol 35 (1) ◽  
pp. 129-149 ◽  
Author(s):  
Matilde Clarissa Malfatti ◽  
Giulia Antoniali ◽  
Marta Codrich ◽  
Silvia Burra ◽  
Giovanna Mangiapane ◽  
...  
Keyword(s):  
Dna Repair ◽  
Base Excision Repair ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Excision Repair ◽  
Dna Lesions ◽  
Cancer Development ◽  
Dna Repair Enzymes ◽  
Repair Enzymes ◽  
Base Excision

Abstract Alterations of DNA repair enzymes and consequential triggering of aberrant DNA damage response (DDR) pathways are thought to play a pivotal role in genomic instabilities associated with cancer development, and are further thought to be important predictive biomarkers for therapy using the synthetic lethality paradigm. However, novel unpredicted perspectives are emerging from the identification of several non-canonical roles of DNA repair enzymes, particularly in gene expression regulation, by different molecular mechanisms, such as (i) non-coding RNA regulation of tumour suppressors, (ii) epigenetic and transcriptional regulation of genes involved in genotoxic responses and (iii) paracrine effects of secreted DNA repair enzymes triggering the cell senescence phenotype. The base excision repair (BER) pathway, canonically involved in the repair of non-distorting DNA lesions generated by oxidative stress, ionising radiation, alkylation damage and spontaneous or enzymatic deamination of nucleotide bases, represents a paradigm for the multifaceted roles of complex DDR in human cells. This review will focus on what is known about the canonical and non-canonical functions of BER enzymes related to cancer development, highlighting novel opportunities to understand the biology of cancer and representing future perspectives for designing new anticancer strategies. We will specifically focus on APE1 as an example of a pleiotropic and multifunctional BER protein.

scholarly journals Contribution of Base Excision Repair, Nucleotide Excision Repair, and DNA Recombination to Alkylation Resistance of the Fission Yeast Schizosaccharomyces pombe

2000 ◽  
Vol 182 (8) ◽  
pp. 2104-2112 ◽  
Author(s):  
Asli Memisoglu ◽  
Leona Samson
Keyword(s):  
Dna Repair ◽  
Schizosaccharomyces Pombe ◽  
Nucleotide Excision Repair ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Dna Recombination ◽  
Nucleotide Excision ◽  
Repair Pathways ◽  
Base Excision

ABSTRACT DNA damage is unavoidable, and organisms across the evolutionary spectrum possess DNA repair pathways that are critical for cell viability and genomic stability. To understand the role of base excision repair (BER) in protecting eukaryotic cells against alkylating agents, we generated Schizosaccharomyces pombe strains mutant for the mag1 3-methyladenine DNA glycosylase gene. We report that S. pombe mag1 mutants have only a slightly increased sensitivity to methylation damage, suggesting that Mag1-initiated BER plays a surprisingly minor role in alkylation resistance in this organism. We go on to show that other DNA repair pathways play a larger role than BER in alkylation resistance. Mutations in genes involved in nucleotide excision repair (rad13) and recombinational repair (rhp51) are much more alkylation sensitive thanmag1 mutants. In addition, S. pombe mutant for the flap endonuclease rad2 gene, whose precise function in DNA repair is unclear, were also more alkylation sensitive thanmag1 mutants. Further, mag1 andrad13 interact synergistically for alkylation resistance, and mag1 and rhp51 display a surprisingly complex genetic interaction. A model for the role of BER in the generation of alkylation-induced DNA strand breaks in S. pombe is discussed.

Roles of base excision repair enzymes Nth1p and Apn2p from Schizosaccharomyces pombe in processing alkylation and oxidative DNA damage

DNA Repair ◽  
2005 ◽  
Vol 4 (11) ◽  
pp. 1270-1280 ◽  
Author(s):  
Takanori Sugimoto ◽  
Emi Igawa ◽  
Haruna Tanihigashi ◽  
Mayumi Matsubara ◽  
Hiroshi Ide ◽  
...  
Keyword(s):  
Dna Damage ◽  
Schizosaccharomyces Pombe ◽  
Base Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Repair Enzymes ◽  
Base Excision

scholarly journals HIV-1 and HIV-2 exhibit divergent interactions with HLTF and UNG2 DNA repair proteins

2016 ◽  
Vol 113 (27) ◽  
pp. E3921-E3930 ◽  
Author(s):  
Kasia Hrecka ◽  
Caili Hao ◽  
Ming-Chieh Shun ◽  
Sarabpreet Kaur ◽  
Selene K. Swanson ◽  
...  
Keyword(s):  
Dna Repair ◽  
Excision Repair ◽  
Host Cells ◽  
Hiv Replication ◽  
Dna Repair Enzymes ◽  
Repair Enzymes ◽  
Dna Repair Proteins ◽  
Base Excision ◽  
High Concentrations ◽  
Hiv 1

HIV replication in nondividing host cells occurs in the presence of high concentrations of noncanonical dUTP, apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3 (APOBEC3) cytidine deaminases, and SAMHD1 (a cell cycle-regulated dNTP triphosphohydrolase) dNTPase, which maintains low concentrations of canonical dNTPs in these cells. These conditions favor the introduction of marks of DNA damage into viral cDNA, and thereby prime it for processing by DNA repair enzymes. Accessory protein Vpr, found in all primate lentiviruses, and its HIV-2/simian immunodeficiency virus (SIV) SIVsm paralogue Vpx, hijack the CRL4DCAF1E3 ubiquitin ligase to alleviate some of these conditions, but the extent of their interactions with DNA repair proteins has not been thoroughly characterized. Here, we identify HLTF, a postreplication DNA repair helicase, as a common target of HIV-1/SIVcpz Vpr proteins. We show that HIV-1 Vpr reprograms CRL4DCAF1E3 to direct HLTF for proteasome-dependent degradation independent from previously reported Vpr interactions with base excision repair enzyme uracil DNA glycosylase (UNG2) and crossover junction endonuclease MUS81, which Vpr also directs for degradation via CRL4DCAF1E3. Thus, separate functions of HIV-1 Vpr usurp CRL4DCAF1E3 to remove key enzymes in three DNA repair pathways. In contrast, we find that HIV-2 Vpr is unable to efficiently program HLTF or UNG2 for degradation. Our findings reveal complex interactions between HIV-1 and the DNA repair machinery, suggesting that DNA repair plays important roles in the HIV-1 life cycle. The divergent interactions of HIV-1 and HIV-2 with DNA repair enzymes and SAMHD1 imply that these viruses use different strategies to guard their genomes and facilitate their replication in the host.

scholarly journals Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients

2020 ◽  
Vol 21 (7) ◽  
pp. 2473 ◽  
Author(s):  
Pavel Vodicka ◽  
Marketa Urbanova ◽  
Pavol Makovicky ◽  
Kristyna Tomasova ◽  
Michal Kroupa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Base Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Sporadic Colorectal Cancer ◽  
Base Excision ◽  
Colorectal Cancer Patients

Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy.

scholarly journals Role of Base Excision “Repair” Enzymes in Erasing Epigenetic Marks from DNA

2016 ◽  
Vol 116 (20) ◽  
pp. 12711-12729 ◽  
Author(s):  
Alexander C. Drohat ◽  
Christopher T. Coey
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Epigenetic Marks ◽  
Repair Enzymes ◽  
Base Excision
Sign in / Sign up

Export Citation Format

Share Document