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组蛋白H2A.Z的一种乙酰化形式调控粟酒裂殖酵母中的染色体结构。

An acetylated form of histone H2A.Z regulates chromosome architecture in Schizosaccharomyces pombe.

作者信息

Kim Hyun-Soo, Vanoosthuyse Vincent, Fillingham Jeffrey, Roguev Assen, Watt Stephen, Kislinger Thomas, Treyer Alex, Carpenter Laura Rocco, Bennett Christopher S, Emili Andrew, Greenblatt Jack F, Hardwick Kevin G, Krogan Nevan J, Bähler Jürg, Keogh Michael-Christopher

机构信息

Department of Cell Biology, Albert Einstein College of Medicine, New York, New York, USA.

出版信息

Nat Struct Mol Biol. 2009 Dec;16(12):1286-93. doi: 10.1038/nsmb.1688. Epub 2009 Nov 15.

Abstract

Histone variant H2A.Z has a conserved role in genome stability, although it remains unclear how this is mediated. Here we demonstrate that the fission yeast Swr1 ATPase inserts H2A.Z (Pht1) into chromatin and Kat5 acetyltransferase (Mst1) acetylates it. Deletion or an unacetylatable mutation of Pht1 leads to genome instability, primarily caused by chromosome entanglement and breakage at anaphase. This leads to the loss of telomere-proximal markers, though telomere protection and repeat length are unaffected by the absence of Pht1. Strikingly, the chromosome entanglement in pht1Delta anaphase cells can be rescued by forcing chromosome condensation before anaphase onset. We show that the condensin complex, required for the maintenance of anaphase chromosome condensation, prematurely dissociates from chromatin in the absence of Pht1. This and other findings suggest an important role for H2A.Z in the architecture of anaphase chromosomes.

摘要

组蛋白变体H2A.Z在基因组稳定性方面具有保守作用,尽管其介导机制尚不清楚。在此我们证明,裂殖酵母Swr1 ATP酶将H2A.Z(Pht1)插入染色质,而Kat5乙酰转移酶(Mst1)使其乙酰化。Pht1的缺失或不可乙酰化突变会导致基因组不稳定,主要原因是后期染色体缠结和断裂。这会导致端粒近端标记物丢失,不过端粒保护和重复长度不受Pht1缺失的影响。引人注目的是,通过在后期开始前促使染色体凝聚,可以挽救pht1Δ后期细胞中的染色体缠结。我们表明,维持后期染色体凝聚所需的凝聚素复合物在缺乏Pht1时会过早地从染色质上解离。这一发现及其他结果表明H2A.Z在后期染色体结构中具有重要作用。

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