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論文
- タイトル
- タイトル（英）
- Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy.
- 参照URL
- https://researchmap.jp/toyonatsume/published_papers/40416823
- 著者
- 著者（英）
- Laura J Grange,John J Reynolds,Farid Ullah,Bertrand Isidor,Robert F Shearer,Xenia Latypova,Ryan M Baxley,Antony W Oliver,Anil Ganesh,Sophie L Cooke,Satpal S Jhujh,Gavin S McNee,Robert Hollingworth,Martin R Higgs,Toyoaki Natsume,Tahir Khan,Gabriel Á Martos-Moreno,Sharon Chupp,Christopher G Mathew,David Parry,Michael A Simpson,Nahid Nahavandi,Zafer Yüksel,Mojgan Drasdo,Anja Kron,Petra Vogt,Annemarie Jonasson,Saad Ahmed Seth,Claudia Gonzaga-Jauregui,Karlla W Brigatti,Alexander P A Stegmann,Masato Kanemaki,Dragana Josifova,Yuri Uchiyama,Yukiko Oh,Akira Morimoto,Hitoshi Osaka,Zineb Ammous,Jesús Argente,Naomichi Matsumoto,Constance T R M Stumpel,Alexander M R Taylor,Andrew P Jackson,Anja-Katrin Bielinsky,Niels Mailand,Cedric Le Caignec,Erica E Davis,Grant S Stewart
- 概要
- 概要（英）
- Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Nature communications
- 巻
- 13
- 号
- 1
- 開始ページ
- 6664
- 終了ページ
- 6664
- 出版年月
- 2022年11月4日
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1038/s41467-022-34349-8
- 共同研究・競争的資金等の研究課題
研究者
夏目 豊彰
(ナツメ トヨアキ)