CiMutT, an asidian MutT homologue, has a 7, 8-dihydro-8-oxo-dGTP pyrophosphohydrolase activity responsible for sanitization of oxidized nucleotides in Ciona intestinalis

Yonekura, Shin Ichiro; Sanada, U.; Zhang-Akiyama, Qiu Mei

doi:10.1266/ggs.85.287

Cited by 3 publications

(2 citation statements)

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“…The ascidian (sea squirt) Ciona intestinalis ( C. intestinalis ) is a widely used model organism in developmental biology [ 24 ]. To study the DNA repair mechanism in early development in C. intestinalis , our group has identified several DNA repair and sanitization genes [ 25 – 27 ]. In this study, to clarify the differences of roles among AP endonucleases, we focused on two candidate AP endonucleases in C. intestinalis , CiAPEX2 and CiP0.…”

Section: Introductionmentioning

confidence: 99%

CiAPEX2 and CiP0, candidates of AP endonucleases in Ciona intestinalis, have 3′-5′ exonuclease activity and contribute to protection against oxidative stress

et al. 2017

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Apurinic/apyrimidinic (AP) sites are one of the most frequent DNA lesions. AP sites inhibit transcription and DNA replication, and induce cell death. AP endonucleases are key enzymes in AP site repair. Several types of AP endonucleases have been reported, such as AP endonuclease 2 (APEX2) and ribosomal protein P0 (P0). However, it is not known how the functions and roles differ among AP endonucleases. To clarify the difference of roles among AP endonucleases, we conducted biochemical analysis focused on APEX2 and P0 homologues in Ciona intestinalis. Amino acid sequence analysis suggested that CiAPEX2 and CiP0 are AP endonuclease homologues. Although we could not detect AP endonuclease or 3′-phosphodiesterase activity, these two purified proteins exhibited 3′-5′ exonuclease activity. This 3′-5′ exonuclease activity was sensitive to ethylenediaminetetraacetic acid (EDTA), and the efficiency of this activity was influenced by the 3′-terminus of substrate DNA. Both CiAPEX2 and CiP0 degraded not only a 5′-protruding DNA end, but also nicked DNA, which is generated through AP endonuclease 1 (APEX1) cleavage. These two genes partially complemented the growth rate of AP endonuclease-deficient Escherichia coli treated with hydrogen peroxide. These results indicate that 3′-5′ exonuclease activity is an evolutionarily conserved enzymatic activity of APEX2 and P0 homologues and this enzymatic activity may be important for AP endonucleases.Electronic supplementary materialThe online version of this article (10.1186/s41021-017-0087-7) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

CiAPEX2 and CiP0, candidates of AP endonucleases in Ciona intestinalis, have 3′-5′ exonuclease activity and contribute to protection against oxidative stress

et al. 2017

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“…As the first step to address the above questions, it is necessary to identify enzymes that are involved in the repair of oxidatively damaged bases in DNA in C. intestinalis. We recently identified several C. intestinalis homologues of BER enzymes, CiOgg1 (Jin et al, 2006) and AP endonucleases (unpublished results), and the sanitization enzyme for oxidized nucleotides, CiMutT (Yonekura et al, 2010). Knockdown of CiOgg1 expression by a Morpholino oligo (RNAi) method resulted in arrest at an early stage during development in C. intestinalis (Jin et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Structural and functional properties of CiNTH, an endonuclease III homologue of the ascidian <i>Ciona intestinalis</i>: critical role of N-terminal region

et al. 2012

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Oxidatively damaged bases in DNA can cause cell death, mutation and/or cancer induction. To overcome such deleterious effects of DNA base oxidation, cells are equipped with base excision repair (BER) initiated by DNA glycosylases. Endonuclease III (Nth), a major DNA glycosylase, mainly excises oxidatively damaged pyrimidines from DNA. The aims of this study were to obtain an overview of the repair mechanism of oxidatively damaged bases and to elucidate the function of BER in maintaining genome stability during embryogenesis and development. In this study, we used the ascidian Ciona intestinalis because at every developmental stage it is possible to observe the phenotype of individuals with DNA damage or mutations. Sequence alignment analysis revealed that the amino acid sequence of Ciona intestinalis Nth homologue (CiNTH) had high homology with those of Escherichia coli, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans and human Nth homologues. It was evident that two domains, the Helix-hairpin-Helix and 4Fe-4S cluster domains that are critical regions for the Nth activity, are well conserved in CiNTH. CiNTH efficiently complemented the sensitivity of E. coli nth nei mutant to H 2 O 2 . CiNTH was bifunctional, with DNA glycosylase and AP lyase activities. It removed thymine glycol, 5-formyluracil and 8-oxoguanine paired with G from DNA via a β-elimination reaction. Interestingly, the N-terminal 44 amino acids were essential for the DNA glycosylase activity of CiNTH.

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Substrate ambiguity among the nudix hydrolases: biologically significant, evolutionary remnant, or both?

McLennan

2012

Cell. Mol. Life Sci.

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Many members of the nudix hydrolase family exhibit considerable substrate multispecificity and ambiguity, which raises significant issues when assessing their functions in vivo and gives rise to errors in database annotation. Several display low antimutator activity when expressed in bacterial tester strains as well as some degree of activity in vitro towards mutagenic, oxidized nucleotides such as 8-oxo-dGTP. However, many of these show greater activity towards other nucleotides such as ADP-ribose or diadenosine tetraphosphate (Ap(4)A). The antimutator activities have tended to gain prominence in the literature, whereas they may in fact represent the residual activity of an ancestral antimutator enzyme that has become secondary to the more recently evolved major activity after gene duplication. Whether any meaningful antimutagenic function has also been retained in vivo requires very careful assessment. Then again, other examples of substrate ambiguity may indicate as yet unexplored regulatory systems. For example, bacterial Ap(4)A hydrolases also efficiently remove pyrophosphate from the 5' termini of mRNAs, suggesting a potential role for Ap(4)A in the control of bacterial mRNA turnover, while the ability of some eukaryotic mRNA decapping enzymes to degrade IDP and dIDP or diphosphoinositol polyphosphates (DIPs) may also be indicative of new regulatory networks in RNA metabolism. DIP phosphohydrolases also degrade diadenosine polyphosphates and inorganic polyphosphates, suggesting further avenues for investigation. This article uses these and other examples to highlight the need for a greater awareness of the possible significance of substrate ambiguity among the nudix hydrolases as well as the need to exert caution when interpreting incomplete analyses.

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CiMutT, an asidian MutT homologue, has a 7, 8-dihydro-8-oxo-dGTP pyrophosphohydrolase activity responsible for sanitization of oxidized nucleotides in Ciona intestinalis

Cited by 3 publications

References 43 publications

CiAPEX2 and CiP0, candidates of AP endonucleases in Ciona intestinalis, have 3′-5′ exonuclease activity and contribute to protection against oxidative stress

CiAPEX2 and CiP0, candidates of AP endonucleases in Ciona intestinalis, have 3′-5′ exonuclease activity and contribute to protection against oxidative stress

Structural and functional properties of CiNTH, an endonuclease III homologue of the ascidian <i>Ciona intestinalis</i>: critical role of N-terminal region

Substrate ambiguity among the nudix hydrolases: biologically significant, evolutionary remnant, or both?

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