Synthesis, DNA Polymerase Incorporation, and Enzymatic Phosphate Hydrolysis of Formamidopyrimidine Nucleoside Triphosphates

Imoto, Shuhei; Patro, Jennifer N.; Jiang, Yu; Oka, Natsuhisa; Greenberg, Marc M.

doi:10.1021/ja065525r

Cited by 22 publications

(34 citation statements)

References 53 publications

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“…Ϫ5 to 10 Ϫ2 of unmodified dNTPs incorporated (110)(111)(112)(113). In fact, one of the most common oxidative modifications in the dNTP pool has been shown to be incorporated almost 24 times more efficiently in complementing A than the opposite template C by human polymerase ␤ (112).…”

Section: Dna Repairmentioning

confidence: 99%

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

Schmoll

Dattenböck

Carreras-Villaseñor

et al. 2016

Microbiol Mol Biol Rev

163

195

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SUMMARYThe genusTrichodermacontains fungi with high relevance for humans, with applications in enzyme production for plant cell wall degradation and use in biocontrol. Here, we provide a broad, comprehensive overview of the genomic content of these species for “hot topic” research aspects, including CAZymes, transport, transcription factors, and development, along with a detailed analysis and annotation of less-studied topics, such as signal transduction, genome integrity, chromatin, photobiology, or lipid, sulfur, and nitrogen metabolism inT. reesei,T. atroviride, andT. virens, and we open up new perspectives to those topics discussed previously. In total, we covered more than 2,000 of the predicted 9,000 to 11,000 genes of eachTrichodermaspecies discussed, which is >20% of the respective gene content. Additionally, we considered available transcriptome data for the annotated genes. Highlights of our analyses include overall carbohydrate cleavage preferences due to the different genomic contents and regulation of the respective genes. We found light regulation of many sulfur metabolic genes. Additionally, a new Golgi 1,2-mannosidase likely involved inN-linked glycosylation was detected, as were indications for the ability ofTrichodermaspp. to generate hybrid galactose-containingN-linked glycans. The genomic inventory of effector proteins revealed numerous compounds unique toTrichoderma, and these warrant further investigation. We found interesting expansions in theTrichodermagenus in several signaling pathways, such as G-protein-coupled receptors, RAS GTPases, and casein kinases. A particularly interesting feature absolutely unique toT. atrovirideis the duplication of the alternative sulfur amino acid synthesis pathway.

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Section: Dna Repairmentioning

confidence: 99%

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

Schmoll

Dattenböck

Carreras-Villaseñor

et al. 2016

Microbiol Mol Biol Rev

163

195

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“…Although WRN does not appear to interact with human OGG1, the major glycosylase for 8-oxodG in human cells, it does interact in vivo and in vitro with NEIL1 [143]. NEIL1 is a human glycosylase for formamidopyrimidine (fapy) lesions [143, 143, 144]. Consistent with this interaction, fapy lesions accumulate in cells deficient in WRN [143].…”

Section: Multiple Roles Of Wrn In Dna Repairmentioning

confidence: 99%

Roles of Werner syndrome protein in protection of genome integrity

2010

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OverviewWerner syndrome protein (WRN) is one of a family of five human RecQ helicases implicated in the maintenance of genome stability. The conserved RecQ family also includes RecQ1, Bloom syndrome protein (BLM), RecQ4, and RecQ5 in humans (see additional reviews in this issue), as well as Sgs1 in Saccharomyces cerevisiae, Rqh1 in Schizosaccharomyces pombe, and homologs in Caenorhabditis elegans, Xenopus laevis, and Drosophila melanogaster [1]. Defects in three of the RecQ helicases, RecQ4, BLM, and WRN, cause human pathologies linked with cancer predisposition and premature aging [1][2][3][4][5]. Mutations in the WRN gene are the causative factor of Werner syndrome (WS). WRN is one of the best characterized of the RecQ helicases and is known to have roles in DNA replication and repair, transcription, and telomere maintenance [1][2][3][4][5][6]. Studies both in vitro and in vivo indicate that the roles of WRN in a variety of DNA processes are mediated by post-translational modifications, as well as several important protein-protein interactions [1,2,7]. Many of these functions of WRN in genome maintenance, as well as the clinical characteristics of WS, have been recently reviewed [8][9][10][11][12]. In this work, we will summarize some of the early studies on the cellular roles of WRN and highlight the recent findings that shed some light on the link between the protein and its cellular functions with the disease pathology. Molecular Genetics of Werner Syndrome (WS)WS is a rare autosomal recessive progeroid disorder characterized by the development of cataracts, changing of skin conditions, bird-like facies, atypical short stature, and premature graying or thinning of the hair [9]. Patients also often develop hypogonadism, osteoporosis, diabetes mellitus, artherosclerosis [13], and cancers, particularly sarcomas [14]. Onset of symptoms usually occurs in the third decade of life, and health subsequently declines with median age at death between 47-54 years [13]. Because WS presents with early-onset of conditions commonly seen in the aged, it is a good model system for the study of mechanisms of normal aging [15,16]. WRN BiochemistryThe causative factor of the majority of WS is mutation in the WRN gene, which codes for a member of the highly conserved RecQ family of helicases. While several different mutations within the gene are seen in WS, most result in production of truncated WRN protein [13]. 1Address correspondence to: Dr. Vilhelm A. Bohr, NIH Biomedical Research Center, 251 Bayview Boulevard, Baltimore, MD 21224; BohrV@grc.nia.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the...

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“…Fapy•dGTP ( k cat / K m = 3.8 ± 1.3 × 10 2 M −1 s −1 ) hydrolysis by MutT is more than 100-fold slower than is dGTP ( k cat / K m = 4.3 ± 0.9 × 10 4 M −1 s −1 ) and greater than 10,000 less efficient than 8-oxodGuoTP ( k cat / K m = 5.4 ± 0.7 × 10 6 M −1 s −1 ). 56 …”

Section: Formamidopyrimidine Lesions’ Effects On Polymerase Enzymementioning

confidence: 99%

The Formamidopyrimidines: Purine Lesions Formed in Competition With 8-Oxopurines From Oxidative Stress

Greenberg

2011

Acc. Chem. Res.

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Conspectus DNA is constantly exposed to agents that induce structural damage, from sources both internal and external to an organism. Endogenous species, such as oxidizing chemicals, and exogenous agents, such as ultraviolet rays in sunlight, together produce more than 70 distinct chemical modifications of native nucleotides. Of these, about 15 of the lesions have been detected in cellular DNA. This kind of structural DNA damage can be cytotoxic, carcinogenic, or both, and is being linked to an increasingly lengthy list of diseases. The formamidopyrimidine (Fapy) lesions are a family of DNA lesions that result after purines undergo oxidative stress. The Fapy lesions are produced in yields comparable to the 8-oxopurines, which, owing in part to a perception of mutagenicity in some quarters, have been subjected to intense research scrutiny. But despite the comparable abundance of the formamidopyrimidines and the 8-oxopurines, until recently very little was known about the effects of Fapy lesions on biochemical processes involving DNA or on the structure and stability of the genomic material. In this Account, we discuss the detection of Fapy lesions in DNA and the mechanism proposed for their formation. We also describe methods for the chemical synthesis of oligonucleotides containing Fapy•dA or Fapy•dG and the outcomes of chemical and biochemical studies utilizing these compounds. These experiments reveal that the formamidopyrimidines decrease the fidelity of polymerases and are substrates for DNA repair enzymes. The mutation frequency of Fapy•dG in mammals is even greater than that of 8-oxodGuo (8-oxo-7,8-dihydro-2′-deoxyguanosine, one of the 8-oxopurines), suggesting that this lesion could be a useful biomarker and biologically significant. Despite clear similarities, the formamidopyrimidines have lived in the shadow of the corresponding 8-oxopurine lesions. But the recent development of methods for synthesizing oligonucleotides containing Fapy•dA or Fapy•dG has accelerated research on these lesions, revealing that the formamidopyrimidines are repaired as efficiently and, in some cases, more rapidly than the 8-oxopurines. Fapy•dG appears to be a lesion of biochemical consequence, and further study of its mutagenicity, repair, and interactions with DNA structure will better define the cellular details involving this important product of DNA stress.

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Synthesis, DNA Polymerase Incorporation, and Enzymatic Phosphate Hydrolysis of Formamidopyrimidine Nucleoside Triphosphates

Cited by 22 publications

References 53 publications

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

Roles of Werner syndrome protein in protection of genome integrity

The Formamidopyrimidines: Purine Lesions Formed in Competition With 8-Oxopurines From Oxidative Stress

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