8-Hydroxyguanine levels and repair capacity during mouse embryonic stem cell differentiation

Kuboyama, Ayumi; Tanaka, Shoichi; Kawai, Kazuaki; Kasai, Hiroshi; Morii, Haruki; Tamae, Kazuyoshi; Nakashima, Tamiji; Hirano, Takeshi

doi:10.3109/10715762.2011.555481

Cited by 9 publications

(8 citation statements)

References 29 publications

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“…A comparison of embryonic stem cells to more differentiated cells did not reveal any impact on the mRNA levels of MUTYH, in contrast to OGG1, which decreased upon differentiation (Kuboyama et al, 2011). Alimentary supplementation with quercetin, a plant-derived flavonoid that has been attributed with anticarcinogen, was found to enhance the expression of MUTYH in the distal colon mucosa of rats (Dihal et al, 2008).…”

Section: Regulation Of Mutyhmentioning

confidence: 99%

MUTYH DNA glycosylase: the rationale for removing undamaged bases from the DNA

Markkanen¹,

Dorn²,

Hübscher³

2013

Front. Genet.

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Maintenance of genetic stability is crucial for all organisms in order to avoid the onset of deleterious diseases such as cancer. One of the many proveniences of DNA base damage in mammalian cells is oxidative stress, arising from a variety of endogenous and exogenous sources, generating highly mutagenic oxidative DNA lesions. One of the best characterized oxidative DNA lesion is 7,8-dihydro-8-oxoguanine (8-oxo-G), which can give rise to base substitution mutations (also known as point mutations). This mutagenicity is due to the miscoding potential of 8-oxo-G that instructs most DNA polymerases (pols) to preferentially insert an Adenine (A) opposite 8-oxo-G instead of the appropriate Cytosine (C). If left unrepaired, such A:8-oxo-G mispairs can give rise to CG→AT transversion mutations. A:8-oxo-G mispairs are proficiently recognized by the MutY glycosylase homologue (MUTYH). MUTYH can remove the mispaired A from an A:8-oxo-G, giving way to the canonical base-excision repair (BER) that ultimately restores undamaged Guanine (G). The importance of this MUTYH-initiated pathway is illustrated by the fact that biallelic mutations in the MUTYH gene are associated with a hereditary colorectal cancer syndrome termed MUTYH-associated polyposis (MAP). In this review, we will focus on MUTYH, from its discovery to the most recent data regarding its cellular roles and interaction partners. We discuss the involvement of the MUTYH protein in the A:8-oxo-G BER pathway acting together with pol λ, the pol that can faithfully incorporate C opposite 8-oxo-G and thus bypass this lesion in a correct manner. We also outline the current knowledge about the regulation of MUTYH itself and the A:8-oxo-G repair pathway by posttranslational modifications (PTM). Finally, to achieve a clearer overview of the literature, we will briefly touch on the rather confusing MUTYH nomenclature. In short, MUTYH is a unique DNA glycosylase that catalyzes the excision of an undamaged base from DNA.

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Section: Regulation Of Mutyhmentioning

confidence: 99%

MUTYH DNA glycosylase: the rationale for removing undamaged bases from the DNA

Markkanen¹,

Dorn²,

Hübscher³

2013

Front. Genet.

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“…Our findings are consistent with previous studies which showed that ROS play crucial roles as secondary messengers during stem cell differentiation into various somatic lineages [10,11], so that an increase in ROS levels in differentiated stem cell progenies is therefore expected. Hirano and Tamae [12] and Kuboyama et al [13], also reported that undifferentiated embryonic stem cells were more resistant to DNA damage induced by the ROS -8-oxoguanine (which is known to generate GC-to-TA point mutations in genomic DNA), as compared to their differentiated progenies. These findings are thus consistent with the results of this study, as well as our previous studies [5,6].…”

Section: Discussionmentioning

confidence: 99%

Differential resistance of human embryonic stem cells and somatic cell types to hydrogen peroxide-induced genotoxicity may be dependent on innate basal intracellular ROS levels

Vinoth

Manikandan

Sethu

et al. 2015

Folia Histochem Cytobiol.

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Previously, we demonstrated that undifferentiated human embryonic stem cells (hESC) displayed higher resistance to oxidative and genotoxic stress compared to somatic cells, but did not further probe the underlying mechanisms. Using H 2 O 2 -induced genotoxicity as a model, this study investigated whether higher resistance of hESC to oxidative and genotoxic stress could be due to lower innate basal intracellular levels of reactive oxygen species (ROS), as compared to their differentiated fibroblastic progenies (H1F) and two other somatic cell types -human embryonic palatal mesenchymal (HEPM) cells and peripheral blood lymphocytes (PBL). Comet assay demonstrated that undifferentiated hESC consistently sustained lower levels of DNA damage upon acute exposure to H 2 O 2 for 30 min, compared to somatic cells. DCFDA and HE staining with flow cytometry showed 170 Kumar Jayaseelan Vinoth et al.

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“…We recently found that the defense capacity against 8-oxo-Gua was also higher in ES cells than in their differentiated counterparts [12]. In the study, we measured the 8-oxo-Gua generation level in the DNA of ES cells and their differentiated counterparts.…”

Section: Differentiation Of Es Cells and Dna Damage / Dna Repair Systemsmentioning

confidence: 97%

“…Our study provided valuable information for the use of stem cells for regenerative medicine in the future. In this short review, we describe oxidative DNA damage and ES cell differentiation, by summarizing our previous work [12] and that of other researchers.…”

Section: A) B)mentioning

confidence: 99%

Differentiation of Embryonic Stem Cells and Oxidative DNA Damage / DNA Repair Systems

Hirano¹,

Tamae²

2012

J Stem Cell Res Ther

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To maintain genomic integrity, cells are equipped with a defense capacity against DNA damage generated in genomic DNA. The avoidance of mutations in genomic DNA is especially critical for undifferentiated cells, such as Embryonic stem (ES) cells. Among the many factors damaging DNA, Reactive Oxidative Species (ROS) are crucial and unavoidable, and thus the roles of ROS in cell differentiation and cellular functions have been extensively studied. However, the biological significance of ROS generation in cell differentiation remains a matter of debate. Among the types of DNA damage due to ROS, 8-oxoguanine (8-oxo-Gua) has been well studied and is known to generate GC-to-TA point mutations in genomic DNA. We recently analyzed the differences in the resistance to 8-oxo-Gua generation between undifferentiated cells and their differentiated counterparts. Our studies indicated that undifferentiated cells were more resistant to 8-oxo-Gua generation, in comparison to differentiated cells. In this short review, we describe the relationship between ES cell differentiation and oxidative DNA damage / DNA repair systems, by summarizing our previous work and that of other researchers.

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8-Hydroxyguanine levels and repair capacity during mouse embryonic stem cell differentiation

Cited by 9 publications

References 29 publications

MUTYH DNA glycosylase: the rationale for removing undamaged bases from the DNA

MUTYH DNA glycosylase: the rationale for removing undamaged bases from the DNA

Differential resistance of human embryonic stem cells and somatic cell types to hydrogen peroxide-induced genotoxicity may be dependent on innate basal intracellular ROS levels

Differentiation of Embryonic Stem Cells and Oxidative DNA Damage / DNA Repair Systems

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