2024\u5e743\u670813\u65e5<\/p>\n
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Abstract<\/strong><\/p>\n Acetaldehyde, a chemical that can cause DNA damage and contribute to cancer, is <\/i>prevalently present in our environment, e.g., in alcohol, tobacco, and food. Although <\/i>aldehyde potentially promotes crosslinking reactions among biological substances <\/i>including DNA, RNA, and proteins, it remains unclear what types of DNA damage are <\/i>caused by acetaldehyde and how they are repaired. In this study, we examined the <\/i>acetaldehyde sensitivity of DNA damage-deficient cells established from the human <\/i>TK6 cell line. Among the mutants, mismatch repair mutants did not show <\/i>hypersensitivity to acetaldehyde, while cells deficient in base and nucleotide excision <\/i>repair pathways increased their sensitivity. We found a delayed repair and <\/i>hypersensitivity in homologous recombination (HR)-deficient cells but not in nonhomologous <\/i>end joining-deficient cells after acetaldehyde treatment. By analyzing the <\/i>formation of acetaldehyde-induced RAD51 foci, which represent HR intermediates, <\/i>HR-deficient cells, but not NHEJ, exhibit delayed repair of acetaldehyde-induced DNA <\/i>damages, compared with wild-type. These results suggest that acetaldehyde causes <\/i>complex DNA damages that require various types of repair pathways. Interestingly, <\/i>mutants deficient in TDP1 and TDP2, which are involved in the removal of protein <\/i>adducts from DNA ends, exhibited hypersensitivity to acetaldehyde. The acetaldehyde <\/i>sensitivity of the double mutant deficient in both TDP1 and RAD54 was similar to that <\/i>of each single mutant. This epistatic relationship between TDP1 and RAD54 suggests <\/i>that the removal of protein-DNA adducts generated by acetaldehyde needs to be <\/i>removed for efficient repair by HR. Our study would help understand the molecular <\/i>mechanism of the genotoxic and mutagenic effects of acetaldehyde.<\/i><\/p>\n KEY WORDS: homologous recombination, acetaldehyde, DNA-protein adducts<\/i><\/p>\n","protected":false},"featured_media":0,"template":"","_links":{"self":[{"href":"https:\/\/www.igakuken.or.jp\/genome\/index.php?rest_route=\/wp\/v2\/new_publication\/4035"}],"collection":[{"href":"https:\/\/www.igakuken.or.jp\/genome\/index.php?rest_route=\/wp\/v2\/new_publication"}],"about":[{"href":"https:\/\/www.igakuken.or.jp\/genome\/index.php?rest_route=\/wp\/v2\/types\/new_publication"}],"wp:attachment":[{"href":"https:\/\/www.igakuken.or.jp\/genome\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=4035"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}