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p21 regulates expression of ECM components and promotes pulmonary fibrosis via CDK4 and Rb. p21 可调节 ECM 成分的表达,并通过 CDK4 和 Rb 促进肺纤维化。
IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-30 DOI: 10.1038/s44318-024-00246-7
Nurit Papismadov, Naama Levi, Lior Roitman, Amit Agrawal, Yossi Ovadya, Ulysse Cherqui, Reut Yosef, Hagay Akiva, Hilah Gal, Valery Krizhanovsky

Fibrosis and accumulation of senescent cells are common tissue changes associated with aging. Here, we show that the CDK inhibitor p21 (CDKN1A), known to regulate the cell cycle and the viability of senescent cells, also controls the expression of extracellular matrix (ECM) components in senescent and proliferating cells of the fibrotic lung, in a manner dependent on CDK4 and Rb phosphorylation. p21 knockout protects mice from the induction of lung fibrosis. Moreover, inducible p21 silencing during fibrosis development alleviates disease pathology, decreasing the inflammatory response and ECM accumulation in the lung, and reducing the amount of senescent cells. Furthermore, p21 silencing limits fibrosis progression even when introduced during disease development. These findings show that one common mechanism regulates both cell cycle progression and expression of ECM components, and suggest that targeting p21 might be a new approach for treating age-related fibrotic pathologies.

纤维化和衰老细胞的积累是与衰老相关的常见组织变化。在这里,我们发现 CDK 抑制剂 p21(CDKN1A)能调节细胞周期和衰老细胞的活力,它还能控制纤维化肺部衰老细胞和增殖细胞中细胞外基质(ECM)成分的表达,其方式依赖于 CDK4 和 Rb 磷酸化。此外,在纤维化发展过程中诱导性沉默 p21 可减轻疾病病理,减少炎症反应和肺部 ECM 的积累,并减少衰老细胞的数量。此外,即使在疾病发展过程中引入 p21 沉默,也能限制纤维化的进展。这些研究结果表明,一种共同的机制同时调控细胞周期的进展和 ECM 成分的表达,并表明以 p21 为靶点可能是治疗与年龄相关的纤维化病症的一种新方法。
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引用次数: 0
Cellular senescence, p21, and the path to fibrosis. 细胞衰老、p21 和纤维化之路。
IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-30 DOI: 10.1038/s44318-024-00245-8
Paolo S Turano, Utz Herbig
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引用次数: 0
The TrkC-PTPσ complex governs synapse maturation and anxiogenic avoidance via synaptic protein phosphorylation. TrkC-PTPσ复合体通过突触蛋白磷酸化调节突触成熟和焦虑性回避。
IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-27 DOI: 10.1038/s44318-024-00252-9
Husam Khaled, Zahra Ghasemi, Mai Inagaki, Kyle Patel, Yusuke Naito, Benjamin Feller, Nayoung Yi, Farin B Bourojeni, Alfred Kihoon Lee, Nicolas Chofflet, Artur Kania, Hidetaka Kosako, Masanori Tachikawa, Steven Connor, Hideto Takahashi

The precise organization of pre- and postsynaptic terminals is crucial for normal synaptic function in the brain. In addition to its canonical role as a neurotrophin-3 receptor tyrosine kinase, postsynaptic TrkC promotes excitatory synapse organization through interaction with presynaptic receptor-type tyrosine phosphatase PTPσ. To isolate the synaptic organizer function of TrkC from its role as a neurotrophin-3 receptor, we generated mice carrying TrkC point mutations that selectively abolish PTPσ binding. The excitatory synapses in mutant mice had abnormal synaptic vesicle clustering and postsynaptic density elongation, more silent synapses, and fewer active synapses, which additionally exhibited enhanced basal transmission with impaired release probability. Alongside these phenotypes, we observed aberrant synaptic protein phosphorylation, but no differences in the neurotrophin signaling pathway. Consistent with reports linking these aberrantly phosphorylated proteins to neuropsychiatric disorders, mutant TrkC knock-in mice displayed impaired social responses and increased avoidance behavior. Thus, through its regulation of synaptic protein phosphorylation, the TrkC-PTPσ complex is crucial for the maturation, but not formation, of excitatory synapses in vivo.

突触前和突触后终端的精确组织对大脑突触功能的正常发挥至关重要。除了作为神经营养素-3受体酪氨酸激酶的典型作用外,突触后TrkC还通过与突触前受体型酪氨酸磷酸酶PTPσ的相互作用促进兴奋性突触的组织。为了将TrkC的突触组织功能与其作为神经营养素-3受体的作用分离开来,我们培育了携带TrkC点突变的小鼠,这种突变选择性地取消了PTPσ的结合。突变小鼠的兴奋性突触具有异常的突触小泡聚集和突触后密度伸长、更多的沉默突触和更少的活跃突触,此外,这些突触还表现出基础传递增强,释放概率受损。除了这些表型,我们还观察到突触蛋白磷酸化异常,但神经营养素信号通路没有差异。与这些异常磷酸化蛋白与神经精神疾病有关的报道一致,突变的TrkC基因敲入小鼠显示出社交反应受损和回避行为增加。因此,通过调节突触蛋白磷酸化,TrkC-PTPσ复合物对兴奋性突触在体内的成熟(而非形成)至关重要。
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引用次数: 0
The human disease-associated gene ZNFX1 controls inflammation through inhibition of the NLRP3 inflammasome. 人类疾病相关基因 ZNFX1 通过抑制 NLRP3 炎性体控制炎症。
IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-27 DOI: 10.1038/s44318-024-00236-9
Jing Huang, Yao Wang, Xin Jia, Changfeng Zhao, Meiqi Zhang, Mi Bao, Pan Fu, Cuiqin Cheng, Ruona Shi, Xiaofei Zhang, Jun Cui, Gang Wan, Anlong Xu

Inherited deficiency of zinc finger NFX1-type containing 1 (ZNFX1), a dsRNA virus sensor, is associated with severe familial immunodeficiency, multisystem inflammatory disease, increased susceptibility to viruses, and early mortality. However, limited treatments for patients with pathological variants of ZNFX1 exist due to an incomplete understanding of the diseases resulting from ZNFX1 mutations. Here, we demonstrate that ZNFX1 specifically inhibits the activation of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome in response to NLRP3 activators both in vitro and in vivo. ZNFX1 retains NLRP3 in the cytoplasm and prevents its accumulation in the TGN38 + /TGN46+ vesicles in the resting state. Upon NLRP3 inflammasome activation, ZNFX1 is cleaved by caspase-1, establishing a feed-forward loop that promotes NLRP3 accumulation in the trans-Golgi network (TGN) and amplifies the activity of the downstream cascade. Expression of wild-type ZNFX1, but not of ZNFX1 with human pathogenic mutations, rescues the impairment of NLRP3 inflammasome inhibition. Our findings reveal a dual role of ZNFX1 in virus sensing and suppression of inflammation, which may become valuable for the development of treatments for ZNFX1 mutation-related diseases.

锌指 NFX1 型含 1(ZNFX1)是一种 dsRNA 病毒传感器,其遗传性缺乏与严重的家族性免疫缺陷、多系统炎症性疾病、对病毒的易感性增加和早期死亡有关。然而,由于对 ZNFX1 基因突变导致的疾病了解不全面,对 ZNFX1 病理变体患者的治疗非常有限。在这里,我们证明了 ZNFX1 能在体外和体内特异性地抑制 NLR 家族含吡咯啉结构域蛋白 3(NLRP3)炎性体对 NLRP3 激活剂的激活。ZNFX1 可将 NLRP3 保留在细胞质中,并防止其在静息状态下积聚在 TGN38 + /TGN46+ 囊泡中。NLRP3炎性体激活后,ZNFX1会被caspase-1裂解,从而建立一个前馈环,促进NLRP3在跨高尔基体网络(TGN)中的积累,并增强下游级联的活性。野生型 ZNFX1 的表达能挽救 NLRP3 炎性体抑制的损伤,但人类致病突变 ZNFX1 的表达则不能。我们的研究结果揭示了 ZNFX1 在病毒感染和抑制炎症中的双重作用,这可能对开发 ZNFX1 突变相关疾病的治疗方法很有价值。
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引用次数: 0
PUFFFIN: an ultra-bright, customisable, single-plasmid system for labelling cell neighbourhoods. PUFFFIN:用于标记细胞邻域的超亮、可定制的单质粒系统。
IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-12 DOI: 10.1038/s44318-024-00154-w
Tamina Lebek, Mattias Malaguti, Giulia Lm Boezio, Lida Zoupi, James Briscoe, Alistair Elfick, Sally Lowell

Cell communication coordinates developmental processes, maintains homeostasis, and contributes to disease. Therefore, understanding the relationship between cells in a shared environment is crucial. Here we introduce Positive Ultra-bright Fluorescent Fusion For Identifying Neighbours (PUFFFIN), a cell neighbour-labelling system based upon secretion and uptake of positively supercharged fluorescent protein s36GFP. We fused s36GFP to mNeonGreen or to a HaloTag, facilitating ultra-bright, sensitive, colour-of-choice labelling. Secretor cells transfer PUFFFIN to neighbours while retaining nuclear mCherry, making identification, isolation, and investigation of live neighbours straightforward. PUFFFIN can be delivered to cells, tissues, or embryos on a customisable single-plasmid construct composed of interchangeable components with the option to incorporate any transgene. This versatility enables the manipulation of cell properties, while simultaneously labelling surrounding cells, in cell culture or in vivo. We use PUFFFIN to ask whether pluripotent cells adjust the pace of differentiation to synchronise with their neighbours during exit from naïve pluripotency. PUFFFIN offers a simple, sensitive, customisable approach to profile non-cell-autonomous responses to natural or induced changes in cell identity or behaviour.

细胞通讯可协调发育过程、维持体内平衡并导致疾病。因此,了解共享环境中细胞之间的关系至关重要。在这里,我们介绍了一种基于正超电荷荧光蛋白 s36GFP 的分泌和吸收的细胞邻居标记系统--正超亮荧光融合识别邻居(PUFFFIN)。我们将 s36GFP 与 mNeonGreen 或 HaloTag 融合,从而实现了超亮、灵敏、颜色可选的标记。分泌细胞将 PUFFFIN 传递给邻近细胞,同时保留核 mCherry,这样就能直接识别、分离和研究活的邻近细胞。PUFFFIN 可以通过一个可定制的单质粒构建体输送到细胞、组织或胚胎中,该构建体由可互换的组件组成,并可选择加入任何转基因。这种多功能性使我们能够在细胞培养或体内操纵细胞特性,同时标记周围的细胞。我们利用 PUFFFIN 来探究多能细胞在脱离幼稚多能性过程中是否会调整分化速度,以便与周围细胞同步。PUFFFIN 提供了一种简单、灵敏、可定制的方法,用于分析细胞对自然或诱导的细胞特性或行为变化的非自主反应。
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引用次数: 0
Modular control of vertebrate axis segmentation in time and space. 脊椎动物轴分节在时间和空间上的模块化控制
IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-09 DOI: 10.1038/s44318-024-00186-2
Ali Seleit, Ian Brettell, Tomas Fitzgerald, Carina Vibe, Felix Loosli, Joachim Wittbrodt, Kiyoshi Naruse, Ewan Birney, Alexander Aulehla

How the timing of development is linked to organismal size is a longstanding question. Although numerous studies have reported a correlation of temporal and spatial traits, the developmental or selective constraints underlying this link remain largely unexplored. We address this question by studying the periodic process of embryonic axis segmentation in-vivo in Oryzias fish. Interspecies comparisons reveal that the timing of segmentation correlates to segment, tissue and organismal size. Segment size in turn scales according to tissue and organism size. To probe for underlying causes, we genetically hybridised two closely related species. Quantitative analysis in ~600 phenotypically diverse F2 embryos reveals a decoupling of timing from size control, while spatial scaling is preserved. Using developmental quantitative trait loci (devQTL) mapping we identify distinct genetic loci linked to either the control of segmentation timing or tissue size. This study demonstrates that a developmental constraint mechanism underlies spatial scaling of axis segmentation, while its spatial and temporal control are dissociable modules.

发育时间如何与生物体大小相关是一个长期存在的问题。尽管许多研究都报道了时间和空间特征的相关性,但这一联系背后的发育或选择性制约因素在很大程度上仍未得到探讨。为了解决这个问题,我们研究了鹗鱼体内胚胎轴分节的周期性过程。种间比较显示,轴的分节时间与分节、组织和生物体的大小相关。节段大小又与组织和生物体大小相关。为了探究其根本原因,我们对两个密切相关的物种进行了基因杂交。对大约 600 个表型不同的 F2 胚胎进行的定量分析显示,时间与大小控制脱钩,而空间比例保持不变。利用发育定量性状位点(devQTL)图谱,我们确定了与分割时间控制或组织大小控制相关的不同遗传位点。这项研究表明,轴分割的空间缩放是发育约束机制的基础,而其空间和时间控制则是可分离的模块。
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引用次数: 0
Structural insights into the molecular effects of the anthelmintics monepantel and betaine on the Caenorhabditis elegans acetylcholine receptor ACR-23. 抗蠕虫药莫奈潘特尔和甜菜碱对优雅尾线虫乙酰胆碱受体 ACR-23 分子影响的结构性启示。
IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-15 DOI: 10.1038/s44318-024-00165-7
Fenglian Liu, Tianyu Li, Huihui Gong, Fei Tian, Yan Bai, Haowei Wang, Chonglin Yang, Yang Li, Fei Guo, Sheng Liu, Qingfeng Chen

Anthelmintics are drugs used for controlling pathogenic helminths in animals and plants. The natural compound betaine and the recently developed synthetic compound monepantel are both anthelmintics that target the acetylcholine receptor ACR-23 and its homologs in nematodes. Here, we present cryo-electron microscopy structures of ACR-23 in apo, betaine-bound, and betaine- and monepantel-bound states. We show that ACR-23 forms a homo-pentameric channel, similar to some other pentameric ligand-gated ion channels (pLGICs). While betaine molecules are bound to the classical neurotransmitter sites in the inter-subunit interfaces in the extracellular domain, monepantel molecules are bound to allosteric sites formed in the inter-subunit interfaces in the transmembrane domain of the receptor. Although the pore remains closed in betaine-bound state, monepantel binding results in an open channel by wedging into the cleft between the transmembrane domains of two neighboring subunits, which causes dilation of the ion conduction pore. By combining structural analyses with site-directed mutagenesis, electrophysiology and in vivo locomotion assays, we provide insights into the mechanism of action of the anthelmintics monepantel and betaine.

抗蠕虫药是用于控制动物和植物中致病蠕虫的药物。天然化合物甜菜碱和最近开发的合成化合物莫奈潘特尔都是针对线虫体内乙酰胆碱受体 ACR-23 及其同源物的抗蠕虫药。在这里,我们展示了ACR-23在apo、与甜菜碱结合以及与甜菜碱和莫奈潘特尔结合状态下的冷冻电镜结构。我们发现,ACR-23 形成了一个同源五聚体通道,类似于其他一些五聚体配体门控离子通道(pLGIC)。甜菜碱分子与细胞外结构域亚基间界面上的经典神经递质位点结合,而莫奈潘特尔分子则与受体跨膜结构域亚基间界面上形成的异构位点结合。虽然在甜菜碱结合状态下孔道仍处于关闭状态,但莫奈潘特尔结合后会楔入两个相邻亚基的跨膜结构域之间的裂隙,从而导致离子传导孔道扩张,从而形成开放通道。通过将结构分析与定点突变、电生理学和体内运动试验相结合,我们深入了解了杀虫药莫奈潘特尔和甜菜碱的作用机制。
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引用次数: 0
Identification of BiP as a temperature sensor mediating temperature-induced germline sex reversal in C. elegans. 鉴定 BiP 作为温度传感器介导温度诱导的秀丽隐杆线虫种系性别逆转。
IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-12 DOI: 10.1038/s44318-024-00197-z
Jing Shi, Danli Sheng, Jie Guo, Fangyuan Zhou, Shaofeng Wu, Hongyun Tang

Sex determination in animals is not only determined by karyotype but can also be modulated by environmental cues like temperature via unclear transduction mechanisms. Moreover, in contrast to earlier views that sex may exclusively be determined by either karyotype or temperature, recent observations suggest that these factors rather co-regulate sex, posing another mechanistic mystery. Here, we discovered that certain wild-isolated and mutant C. elegans strains displayed genotypic germline sex determination (GGSD), but with a temperature-override mechanism. Further, we found that BiP, an ER chaperone, transduces temperature information into a germline sex-governing signal, thereby enabling the coexistence of GGSD and temperature-dependent germline sex determination (TGSD). At the molecular level, increased ER protein-folding requirements upon increased temperatures lead to BiP sequestration, resulting in ERAD-dependent degradation of the oocyte fate-driving factor, TRA-2, thus promoting male germline fate. Remarkably, experimentally manipulating BiP or TRA-2 expression allows to switch between GGSD and TGSD. Physiologically, TGSD allows C. elegans hermaphrodites to maintain brood size at warmer temperatures. Moreover, BiP can also influence germline sex determination in a different, non-hermaphroditic nematode species. Collectively, our findings identify thermosensitive BiP as a conserved temperature sensor in TGSD, and provide mechanistic insights into the transition between GGSD and TGSD.

动物的性别决定不仅由核型决定,还可以通过不明确的传导机制受温度等环境线索的调节。此外,与早期认为性别可能完全由核型或温度决定的观点不同,最近的观察表明,这些因素反而共同调控性别,提出了另一个机理之谜。在这里,我们发现某些野生分离株和突变株的秀丽隐杆线虫表现出基因型生殖系性别决定(GGSD),但具有温度覆盖机制。此外,我们还发现ER伴侣蛋白BiP能将温度信息转化为种系性别控制信号,从而使GGSD和温度依赖性种系性别决定(TGSD)共存。在分子水平上,温度升高对ER蛋白折叠的要求增加,导致BiP螯合,导致ERAD依赖性地降解卵母细胞命运驱动因子TRA-2,从而促进雄性生殖系的命运。值得注意的是,通过实验操纵 BiP 或 TRA-2 的表达可以在 GGSD 和 TGSD 之间切换。从生理学角度看,TGSD能让优雅雌雄同体在较高温度下保持育雏规模。此外,在不同的非雌雄同体线虫物种中,BiP 也能影响生殖细胞的性别决定。总之,我们的研究发现热敏性 BiP 是 TGSD 中一种保守的温度传感器,并为 GGSD 和 TGSD 之间的转变提供了机理上的见解。
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引用次数: 0
Reactive oxygen species activate the Drosophila TNF receptor Wengen for damage-induced regeneration. 活性氧激活果蝇 TNF 受体 Wengen,促进损伤诱导的再生。
IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-17 DOI: 10.1038/s44318-024-00155-9
José Esteban-Collado, Mar Fernández-Mañas, Manuel Fernández-Moreno, Ignacio Maeso, Montserrat Corominas, Florenci Serras

Tumor necrosis factor receptors (TNFRs) control pleiotropic pro-inflammatory functions that range from apoptosis to cell survival. The ability to trigger a particular function will depend on the upstream cues, association with regulatory complexes, and downstream pathways. In Drosophila melanogaster, two TNFRs have been identified, Wengen (Wgn) and Grindelwald (Grnd). Although several reports associate these receptors with JNK-dependent apoptosis, it has recently been found that Wgn activates a variety of other functions. We demonstrate that Wgn is required for survival by protecting cells from apoptosis. This is mediated by dTRAF1 and results in the activation of p38 MAP kinase. Remarkably, Wgn is required for apoptosis-induced regeneration and is activated by the reactive oxygen species (ROS) produced following apoptosis. This ROS activation is exclusive for Wgn, but not for Grnd, and can occur after knocking down Eiger/TNFα. The extracellular cysteine-rich domain of Grnd is much more divergent than that of Wgn, which is more similar to TNFRs from other animals, including humans. Our results show a novel TNFR function that responds to stressors by ensuring p38-dependent regeneration.

肿瘤坏死因子受体(TNFR)控制着从细胞凋亡到细胞存活的多种促炎功能。触发特定功能的能力取决于上游线索、与调控复合物的关联以及下游途径。在黑腹果蝇中,发现了两种 TNFR 受体,即 Wengen(Wgn)和 Grindelwald(Grnd)。尽管一些报道称这些受体与依赖于 JNK 的细胞凋亡有关,但最近发现 Wgn 还能激活多种其他功能。我们证明,Wgn 是保护细胞免于凋亡的生存所必需的。这是由 dTRAF1 介导的,并导致 p38 MAP 激酶的激活。值得注意的是,Wgn 是细胞凋亡诱导再生所必需的,并被细胞凋亡后产生的活性氧(ROS)激活。这种 ROS 激活对 Wgn 而言是唯一的,但对 Grnd 则不是,而且在敲除 Eiger/TNFα 后也会发生。与Wgn相比,Grnd的富半胱氨酸胞外结构域差异更大,而Wgn与其他动物(包括人类)的TNFR更相似。我们的研究结果表明了一种新的TNFR功能,它通过确保p38依赖性再生来应对压力。
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引用次数: 0
CMG helicase disassembly is essential and driven by two pathways in budding yeast. 在芽殖酵母中,CMG 螺旋酶的分解是必不可少的,并由两种途径驱动。
IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-22 DOI: 10.1038/s44318-024-00161-x
Cristian Polo Rivera, Tom D Deegan, Karim P M Labib

The CMG helicase is the stable core of the eukaryotic replisome and is ubiquitylated and disassembled during DNA replication termination. Fungi and animals use different enzymes to ubiquitylate the Mcm7 subunit of CMG, suggesting that CMG ubiquitylation arose repeatedly during eukaryotic evolution. Until now, it was unclear whether cells also have ubiquitin-independent pathways for helicase disassembly and whether CMG disassembly is essential for cell viability. Using reconstituted assays with budding yeast CMG, we generated the mcm7-10R allele that compromises ubiquitylation by SCFDia2. mcm7-10R delays helicase disassembly in vivo, driving genome instability in the next cell cycle. These data indicate that defective CMG ubiquitylation explains the major phenotypes of cells lacking Dia2. Notably, the viability of mcm7-10R and dia2∆ is dependent upon the related Rrm3 and Pif1 DNA helicases that have orthologues in all eukaryotes. We show that Rrm3 acts during S-phase to disassemble old CMG complexes from the previous cell cycle. These findings indicate that CMG disassembly is essential in yeast cells and suggest that Pif1-family helicases might have mediated CMG disassembly in ancestral eukaryotes.

CMG螺旋酶是真核生物复制体的稳定核心,在DNA复制终止时被泛素化和分解。真菌和动物使用不同的酶对CMG的Mcm7亚基进行泛素化,这表明CMG泛素化在真核生物进化过程中反复出现。直到现在,人们还不清楚细胞是否也有不依赖泛素的螺旋酶分解途径,也不清楚CMG分解是否是细胞存活的必要条件。我们利用芽殖酵母 CMG 的重组实验,产生了 mcm7-10R 等位基因,它损害了 SCFDia2 的泛素化作用。mcm7-10R 在体内延迟了螺旋酶的分解,导致下一个细胞周期中基因组的不稳定性。这些数据表明,CMG泛素化缺陷解释了缺乏Dia2的细胞的主要表型。值得注意的是,mcm7-10R 和 dia2∆ 的活力依赖于相关的 Rrm3 和 Pif1 DNA 螺旋酶,它们在所有真核生物中都有直向同源物。我们发现,Rrm3 在 S 期的作用是分解上一个细胞周期的旧 CMG 复合物。这些发现表明,CMG的分解在酵母细胞中是必不可少的,并表明Pif1家族螺旋酶可能在真核生物的祖先中介导了CMG的分解。
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引用次数: 0
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