Role of MUTYH and MSH2 in the Control of Oxidative DNA Damage, Genetic Instability, and Tumorigenesis

Russo, Maria Teresa; Luca, Gabriele De; Casorelli, Ida; Degan, Paolo; Molatore, Sara; Barone, Flavia; Mazzei, Filomena; Pannellini, Tania; Musiani, Piero; Bignami, Margherita

doi:10.1158/0008-5472.can-08-3292

Cited by 49 publications

(44 citation statements)

References 51 publications

(51 reference statements)

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“…In agreement with the important role of MutYH in the repair of oxidative DNA damage, mouse embryonic fibroblasts as well as embryonic stem cells derived from MutYH Ϫ/Ϫ mice show an increase in mutation frequency (6,7). Furthermore, knock-out mice have a higher incidence of tumor formation compared with the wild type mice.…”

supporting

confidence: 57%

Regulation of Human MutYH DNA Glycosylase by the E3 Ubiquitin Ligase Mule

Dorn

Ferrari

Imhof

et al. 2014

Journal of Biological Chemistry

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Background: Regulation of MutYH DNA glycosylase is essential for genomic integrity. Results: MutYH is ubiquitinated by the E3 ligase Mule changing its protein levels and recruitment to chromatin. MutYH levels in cancer cells influence the mutagenic potential of reactive oxygen species. Conclusion: Ubiquitination of MutYH is an important regulatory step. Significance: We identified the residues that are targets for ubiquitination by Mule.

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supporting

confidence: 57%

Regulation of Human MutYH DNA Glycosylase by the E3 Ubiquitin Ligase Mule

Dorn

Ferrari

Imhof

et al. 2014

Journal of Biological Chemistry

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“…In vitro studies support recognition of mismatched 8-oxoG by hMutSα [109]. Studies in S. cerevisiae and human cells support redundant but distinct roles for MSH2 and a BER glycosylase, MutY homolog (MYH), that removes A opposite 8-oxoG [110,111]). In addition, a physical and functional interaction between hMutSα and MYH has been reported [112].…”

Section: Oxidative Damage and Dna Adductsmentioning

confidence: 99%

DNA mismatch repair and the DNA damage response

2016

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This review discusses the role of DNA mismatch repair (MMR) in the DNA damage response (DDR) that triggers cell cycle arrest and, in some cases, apoptosis. Although the focus is on findings from mammalian cells, much has been learned from studies in other organisms including bacteria and yeast [1,2]. MMR promotes a DDR mediated by a key signaling kinase, ATM and Rad3-related (ATR), in response to various types of DNA damage including some encountered in widely used chemotherapy regimes. An introduction to the DDR mediated by ATR reveals its immense complexity and highlights the many biological and mechanistic questions that remain. Recent findings and future directions are highlighted.

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“…Second, in a set of studies that crossed MutY 2/2 mice with a cancer-prone mismatchrepair deficient mouse model (Msh2 2/2 ), compound deletion of both MUTY and MSH2 resulted in a significant increase in 8-oxoG in multiple tissues, compared to MUTY or MSH2 single deletions. However, while Msh2 2/2 mice were prone to lymphomas, further deletion of MUTY was actually protective against development of lymphomas in double knockout mice [Russo et al, 2009]. These results indicate that 8-oxoG accumulation, alone, may be not a strong predictor of carcinogenicity in mouse models.…”

Section: Actions Of Ber Glycosylases In Disease States Obesity and Mementioning

confidence: 99%

Oxidative DNA damage in disease—Insights gained from base excision repair glycosylase‐deficient mouse models

Sampath

2014

Environ and Mol Mutagen

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Cellular components, including nucleic acids, are subject to oxidative damage. If left unrepaired, this damage can lead to multiple adverse cellular outcomes, including increased mutagenesis and cell death. The major pathway for repair of oxidative base lesions is the base excision repair pathway, catalyzed by DNA glycosylases with overlapping but distinct substrate specificities. To understand the role of these glycosylases in the initiation and progression of disease, several transgenic mouse models have been generated to carry a targeted deletion or overexpression of one or more glycosylases. This review summarizes some of the major findings from transgenic animal models of altered DNA glycosylase expression, especially as they relate to pathologies ranging from metabolic disease and cancer to inflammation and neuronal health. Environ. Mol. Mutagen. 55:689-703, 2014. V C 2014 Wiley Periodicals, Inc.

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Role of MUTYH and MSH2 in the Control of Oxidative DNA Damage, Genetic Instability, and Tumorigenesis

Abstract: Mismatch repair is the major pathway controlling genetic stability by removing mispairs caused by faulty replication and/or mismatches containing oxidized bases. Thus,

Cited by 49 publications

References 51 publications

Regulation of Human MutYH DNA Glycosylase by the E3 Ubiquitin Ligase Mule

Regulation of Human MutYH DNA Glycosylase by the E3 Ubiquitin Ligase Mule

DNA mismatch repair and the DNA damage response

Oxidative DNA damage in disease—Insights gained from base excision repair glycosylase‐deficient mouse models

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