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論文
- タイトル
- タイトル（英）
- Mitomycin C-induced DNA double-strand breaks are enhanced by catalytical inactivation of DNA polymerase κ in mice.
- 参照URL
- https://researchmap.jp/213_nk/published_papers/52697525
- 著者
- 著者（英）
- Naoko A Wada,Akira Takeiri,Shigeki Motoyama,Kaori Matsuzaki,Kenji Tanaka,Saori Matsuo,Etsuko Fujii-Takeiri,Hiromi Tateishi,Kaoru Matsumoto,Naoko Niimi,Akira Sassa,Petr Grúz,Kenichi Masumura,Masayuki Mishima,Kou-Ichi Jishage,Kei-Ichi Sugiyama,Takehiko Nohmi
- 担当区分
- 概要
- 概要（英）
- BACKGROUND: DNA polymerase κ (Polk), a member of Y-family DNA polymerases, plays an important role in translesion DNA synthesis (TLS), allowing DNA replication forks to bypass DNA damage or DNA adducts to continue daughter strand synthesis. Polk is also believed to contribute to the replication-independent repair of DNA lesions such as cross-links. TLS circumvents stalls of DNA replication and promotes gap filling in DNA repair which would otherwise result in DNA double-strand breaks (DSBs) and cell death. Mitomycin C (MMC) is a widely used chemotherapeutic drug which generates DNA cross-links and induces DSBs. To clarify how Polk contributes to the prevention of MMC-induced DSB in various organs or tissues, immunohistochemical staining of γH2AX was conducted in catalytically inactivated Polk knock-in (Polk KI) mice and Polk wild-type (Polk+) mice treated with MMC or saline. RESULTS: The γH2AX induction by MMC was enhanced by inactivation of Polk across many organs or tissues to varying degrees. Obvious enhancement was observed in liver, bladder, adrenal cortex, thyroid, and spermatids, whereas less enhancement was shown in brain and retina. The results suggest that Polk plays a role in preventing DSBs caused by MMC in most organs or tissues. Elevated DSB frequencies were observed in both proliferative cells, such as bladder epithelium cells, and less or slowly proliferative cells, such as hepatocytes. Increased DSB levels in inactivated Polk KI mice relative to Polk+ mice were also observed in saline-treated mice in the adrenal cortex and other tissues. CONCLUSION: Polk plays a systemic role in mitigating MMC-induced DSBs, likely through both DNA replication-dependent and -independent mechanisms. Furthermore, Polk appears to protect against DSBs caused by endogenous mutagens in some organs such as the adrenal cortex, prostate, and retina.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Genes and environment : the official journal of the Japanese Environmental Mutagen Society
- 巻
- 47
- 号
- 1
- 開始ページ
- 22
- 終了ページ
- 22
- 出版年月
- 2025年11月6日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1186/s41021-025-00343-x
- 共同研究・競争的資金等の研究課題
研究者
新見 直子
(ニイミ ナオコ)