A Combination of Direct Reversion and Nucleotide Excision Repair Counters the Mutagenic Effects of DNA Carboxymethylation

Overview

Journal DNA Repair (Amst)

Publisher Elsevier

Specialties Biochemistry
Molecular Biology

Date 2022 Jan 14

PMID 35030424

Authors

Claudia M N Aloisi

Nora A Escher

Hyun Suk Kim

Susanne M Geisen

Gabriele A Fontana

Jung-Eun Yeo

Orlando D Scharer

Shana J Sturla

Affiliations

Soon will be listed here.

Abstract

Distinct cellular DNA damage repair pathways maintain the structural integrity of DNA and protect it from the mutagenic effects of genotoxic exposures and processes. The occurrence of O-carboxymethylguanine (O-CMG) has been linked to meat consumption and hypothesized to contribute to the development of colorectal cancer. However, the cellular fate of O-CMG is poorly characterized and there is contradictory data in the literature as to how repair pathways may protect cells from O-CMG mutagenicity. To better address how cells detect and remove O-CMG, we evaluated the role of two DNA repair pathways in counteracting the accumulation and toxic effects of O-CMG. We found that cells deficient in either the direct repair protein O-methylguanine-DNA methyltransferase (MGMT), or key components of the nucleotide excision repair (NER) pathway, accumulate higher levels O-CMG DNA adducts than wild type cells. Furthermore, repair-deficient cells were more sensitive to carboxymethylating agents and displayed an increased mutation rate. These findings suggest that a combination of direct repair and NER circumvent the effects O-CMG DNA damage.

Citing Articles

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