MutY-glycosylase: An overview on mutagenesis and activities beyond the GO system

Oliveira, A.L. de; Silva, Acarizia Eduardo da; Oliveira, Iuri Marques de; Henriques, João Antônio Pêgas; Agnez-Lima, Lucymara Fassarella

doi:10.1016/j.mrfmmm.2014.08.002

Cited by 19 publications

(22 citation statements)

References 132 publications

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“…The activity of Eco LigA at the 3′ A:oxoG nick is in tune with the pro-mutagenic properties of certain DNA polymerases that copy over template oxoG sites to generate A:oxoG configurations ( 54 ). E. coli and many other bacteria have a MutY glycosylase that excises the A nucleobase at an A:oxoG pair to yield an abasic:oxoG lesion, which then undergoes incision and removal of the abasic site, single-nucleotide gap filling by a polymerase to form a 3′ C:oxoG (or 3′ A:oxoG) nick, and subsequent ligation ( 55 ). [A 3′ C:oxoG product can undergo a second round of base excision repair by the MutM glycosylase, which removes the oxoG base ( 55 ).]…”

Section: Discussionmentioning

confidence: 99%

“…E. coli and many other bacteria have a MutY glycosylase that excises the A nucleobase at an A:oxoG pair to yield an abasic:oxoG lesion, which then undergoes incision and removal of the abasic site, single-nucleotide gap filling by a polymerase to form a 3′ C:oxoG (or 3′ A:oxoG) nick, and subsequent ligation ( 55 ). [A 3′ C:oxoG product can undergo a second round of base excision repair by the MutM glycosylase, which removes the oxoG base ( 55 ).] Our data indicate that Eco LigA–AMP is faster at sealing the 3′ A:oxoG nick than the 3′ C:oxoG nick under single-turnover conditions.…”

Section: Discussionmentioning

confidence: 99%

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Kinetic mechanism and fidelity of nick sealing byEscherichia coliNAD⁺-dependent DNA ligase (LigA)

Chauleau

Shuman

2016

Nucleic Acids Res

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Escherichia coli DNA ligase (EcoLigA) repairs 3′-OH/5′-PO4 nicks in duplex DNA via reaction of LigA with NAD+ to form a covalent LigA-(lysyl-Nζ)–AMP intermediate (step 1); transfer of AMP to the nick 5′-PO4 to form an AppDNA intermediate (step 2); and attack of the nick 3′-OH on AppDNA to form a 3′-5′ phosphodiester (step 3). A distinctive feature of EcoLigA is its stimulation by ammonium ion. Here we used rapid mix-quench methods to analyze the kinetic mechanism of single-turnover nick sealing by EcoLigA–AMP. For substrates with correctly base-paired 3′-OH/5′-PO4 nicks, kstep2 was fast (6.8–27 s−1) and similar to kstep3 (8.3–42 s−1). Absent ammonium, kstep2 and kstep3 were 48-fold and 16-fold slower, respectively. EcoLigA was exquisitely sensitive to 3′-OH base mispairs and 3′ N:abasic lesions, which elicited 1000- to >20000-fold decrements in kstep2. The exception was the non-canonical 3′ A:oxoG configuration, which EcoLigA accepted as correctly paired for rapid sealing. These results underscore: (i) how EcoLigA requires proper positioning of the nick 3′ nucleoside for catalysis of 5′ adenylylation; and (ii) EcoLigA's potential to embed mutations during the repair of oxidative damage. EcoLigA was relatively tolerant of 5′-phosphate base mispairs and 5′ N:abasic lesions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Kinetic mechanism and fidelity of nick sealing byEscherichia coliNAD⁺-dependent DNA ligase (LigA)

Chauleau

Shuman

2016

Nucleic Acids Res

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“…Dhillon et al 2011). Costa et al (2015) investigated polymorphisms of three genes, XRCC1, PARP1 and MUTYG , which participate in the BER pathway (Dhillon et al 2011), and XRCC3 , which participates in the HR pathway (de Oliveira et al 2014); mean exposures were up to 1.39 ppm and peak exposures up to 3.2 ppm. The investigated endpoints included CAs, aneuploidies, aberrant cells, multi-aberrant cells and percentage of DNA in the comet tail.…”

Section: Genotoxicitymentioning

confidence: 99%

Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment

2016

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In 2010, the World Health Organization (WHO) established an indoor air quality guideline for short- and long-term exposures to formaldehyde (FA) of 0.1 mg/m3 (0.08 ppm) for all 30-min periods at lifelong exposure. This guideline was supported by studies from 2010 to 2013. Since 2013, new key studies have been published and key cancer cohorts have been updated, which we have evaluated and compared with the WHO guideline. FA is genotoxic, causing DNA adduct formation, and has a clastogenic effect; exposure–response relationships were nonlinear. Relevant genetic polymorphisms were not identified. Normal indoor air FA concentrations do not pass beyond the respiratory epithelium, and therefore FA’s direct effects are limited to portal-of-entry effects. However, systemic effects have been observed in rats and mice, which may be due to secondary effects as airway inflammation and (sensory) irritation of eyes and the upper airways, which inter alia decreases respiratory ventilation. Both secondary effects are prevented at the guideline level. Nasopharyngeal cancer and leukaemia were observed inconsistently among studies; new updates of the US National Cancer Institute (NCI) cohort confirmed that the relative risk was not increased with mean FA exposures below 1 ppm and peak exposures below 4 ppm. Hodgkin’s lymphoma, not observed in the other studies reviewed and not considered FA dependent, was increased in the NCI cohort at a mean concentration ≥0.6 mg/m3 and at peak exposures ≥2.5 mg/m3; both levels are above the WHO guideline. Overall, the credibility of the WHO guideline has not been challenged by new studies.

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“…These various aspects of MUTYH collectively accentuate how the structure and function of MutY and MUTYH elegantly tie to their activities in the cell and the ever-unraveling roles they play in protecting life from DNA damage. Of note, in this review, we highlight primarily new studies and therefore direct the reader to previous reviews on MutY, MUTYH and MAP for additional details [12, 20-27]. …”

Section: Introduction: Muty’s Nobel Heritagementioning

confidence: 99%

Repair of 8-oxoG:A mismatches by the MUTYH glycosylase: Mechanism, metals and medicine

Banda

Nuñez

Burnside

et al. 2017

Free Radical Biology and Medicine

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Reactive oxygen and nitrogen species (RONS) may infringe on the passing of pristine genetic information by inducing DNA inter- and intra-strand crosslinks, protein-DNA crosslinks, and chemical alterations to the sugar or base moieties of DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the most prevalent DNA lesions formed by RONS and is repaired through the base excision repair (BER) pathway involving the DNA repair glycosylases OGG1 and MUTYH in eukaryotes. MUTYH removes adenine (A) from 8-oxoG:A mispairs, thus mitigating the potential of G:C to T:A transversion mutations from occurring in the genome. The paramount role of MUTYH in guarding the genome is well established in the etiology of a colorectal cancer predisposition syndrome involving variants of MUTYH, referred to as MUTYH-associated polyposis. In this review, we highlight recent advances in understanding how MUTYH structure and related function participate in the manifestation of human disease such as MAP. Here we focus on the importance of MUTYH’s metal cofactor sites, including a recently discovered “Zinc linchpin” motif, as well as updates to the catalytic mechanism. Finally, we touch on the insight gleaned from studies with MAP-associated MUTYH variants and recent advances in understanding the multifaceted roles of MUTYH in the cell, both in the prevention of mutagenesis and tumorigenesis.

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MutY-glycosylase: An overview on mutagenesis and activities beyond the GO system

Cited by 19 publications

References 132 publications

Kinetic mechanism and fidelity of nick sealing byEscherichia coliNAD⁺-dependent DNA ligase (LigA)

Kinetic mechanism and fidelity of nick sealing byEscherichia coliNAD⁺-dependent DNA ligase (LigA)

Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment

Repair of 8-oxoG:A mismatches by the MUTYH glycosylase: Mechanism, metals and medicine

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MutY-glycosylase: An overview on mutagenesis and activities beyond the GO system

Cited by 19 publications

References 132 publications

Kinetic mechanism and fidelity of nick sealing byEscherichia coliNAD+-dependent DNA ligase (LigA)

Kinetic mechanism and fidelity of nick sealing byEscherichia coliNAD+-dependent DNA ligase (LigA)

Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment

Repair of 8-oxoG:A mismatches by the MUTYH glycosylase: Mechanism, metals and medicine

Contact Info

Product

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Kinetic mechanism and fidelity of nick sealing byEscherichia coliNAD⁺-dependent DNA ligase (LigA)

Kinetic mechanism and fidelity of nick sealing byEscherichia coliNAD⁺-dependent DNA ligase (LigA)