研究揭示基因組如何應對機械壓力帶來的損傷
作者:
小柯機器人發布時間:2020/4/20 12:57:32
近日,芬蘭赫爾辛基大學Sara A. Wickström團隊發現,異染色質驅動的核軟化能夠保護基因組免受機械壓力引起的損傷。2020年4月16日,《細胞》雜誌在線發表了這項成果。
研究人員發現,機械拉伸使細胞核變形,而細胞最初通過由H3K9me3標記異染色質的丟失來驅動鈣離子依賴性核軟化抵消。染色質流變學和結構的最終變化需要隔離遺傳物質與機械力。未能實現這種核機械力反應會導致DNA損傷。
持續的高振幅拉伸會誘導組織的細胞超對齊,從而在到達核之前重新分配機械能。這種組織範圍的機械適應通過細胞-細胞接觸介導的獨立途徑起作用,並使得細胞/組織關閉核機械轉導以恢復初始染色質狀態。
這項工作確定了染色質在響應形變時,改變自身的機械狀態來維持基因組完整性方面的非經典作用。
據介紹,組織穩態需要在壓力下維持功能完整性。壓力的主要來源是機械力,其作用於細胞、細胞核和染色質,但如何保護基因組免受機械壓力尚不清楚。
附:英文原文
Title: Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage
Author: Michele M. Nava, Yekaterina A. Miroshnikova, Leah C. Biggs, Daniel B. Whitefield, Franziska Metge, Jorge Boucas, Helena Vihinen, Eija Jokitalo, Xinping Li, Juan Manuel García Arcos, Bernd Hoffmann, Rudolf Merkel, Carien M. Niessen, Kris Noel Dahl, Sara A. Wickstrm
Issue&Volume: 2020-04-16
Abstract: Tissue homeostasis requires maintenance of functional integrity under stress. A central source of stress is mechanical force that acts on cells, their nuclei, and chromatin, but how the genome is protected against mechanical stress is unclear. We show that mechanical stretch deforms the nucleus, which cells initially counteract via a calcium-dependent nuclear softening driven by loss of H3K9me3-marked heterochromatin. The resulting changes in chromatin rheology and architecture are required to insulate genetic material from mechanical force. Failure to mount this nuclear mechanoresponse results in DNA damage. Persistent, high-amplitude stretch induces supracellular alignment of tissue to redistribute mechanical energy before it reaches the nucleus. This tissue-scale mechanoadaptation functions through a separate pathway mediated by cell-cell contacts and allows cells/tissues to switch off nuclear mechanotransduction to restore initial chromatin state. Our work identifies an unconventional role of chromatin in altering its own mechanical state to maintain genome integrity in response to deformation.
DOI: 10.1016/j.cell.2020.03.052
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30345-7
Cell:《細胞》,創刊於1974年。隸屬於細胞出版社,最新IF:36.216