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論文
- タイトル
- タイトル（英）
- FANCD2-associated nuclease 1 partially compensates for the lack of Exonuclease 1 in mismatch repair.
- 参照URL
- https://researchmap.jp/7000009079/published_papers/34912785
- 著者
- 著者（英）
- Katja Kratz,Mariela Artola-Borán,Saho Kobayashi-Era,Gene Koh,Goncalo Oliveira,Shunsuke Kobayashi,Andreia Oliveira,Xueqing Zou,Julia Richter,Masataka Tsuda,Hiroyuki Sasanuma,Shunichi Takeda,Joanna I. Loizou,Alessandro A. Sartori,Serena Nik-Zainal,Josef Jiricny
- 担当区分
- 概要
- 概要（英）
- Germline mutations in the mismatch repair (
MM R) genesMSH2 ,MSH6 ,MLH1 andPMS2 are linked to cancer of the colon and other organs, characterised by microsatellite instability and a large increase in mutation frequency. Unexpectedly, mutations inEXO1 , encoding the only exonuclease genetically implicated in MMR, are not linked to familial cancer and cause a substantially weaker mutator phenotype. This difference could be explained if eukaryotic cells possessed additional exonucleases redundant with EXO1. Analysis of the MLH1 interactome identified FANCD2-associated nuclease 1 (FAN1), a novel enzyme with biochemical properties resembling EXO1. We now show that FAN1 efficiently substitutes for EXO1 in MMR assays and that this functional complementation is modulated by its interaction with MLH1. FAN1 also contributes towards MMRin vivo : cells lacking both EXO1 and FAN1 have a MMR defect and display resistance toN -methyl-N -nitrosourea (MNU) and 6-thioguanine (TG). Moreover, FAN1 loss amplifies the mutational profile of EXO1-deficient cells, implying that the two nucleases act redundantly in the same antimutagenic pathway. However, the increased drug resistance and mutator phenotype of FAN1/EXO1-deficient cells are less prominent than those seen in cells lacking MSH6 or MLH1. Eukaryotic cells thus apparently possess additional mechanisms that compensate for the loss of EXO1. - 出版者・発行元
- 出版者・発行元（英）
- American Society for Microbiology
- 誌名
- 誌名（英）
- Molecular and Cellular Biology
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2021年7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
- 0270-7306
- DOI URL
- https://doi.org/10.1128/mcb.00303-21
- 共同研究・競争的資金等の研究課題
研究者
笹沼 博之
( )