Abstract:
:Separation of eukaryotic sister chromatids during the cell cycle is timed by the spindle assembly checkpoint (SAC) and ultimately triggered when separase cleaves cohesion-mediating cohesin1-3. Silencing of the SAC during metaphase activates the ubiquitin ligase APC/C (anaphase-promoting complex, also known as the cyclosome) and results in the proteasomal destruction of the separase inhibitor securin1. In the absence of securin, mammalian chromosomes still segregate on schedule, but it is unclear how separase is regulated under these conditions4,5. Here we show that human shugoshin 2 (SGO2), an essential protector of meiotic cohesin with unknown functions in the soma6,7, is turned into a separase inhibitor upon association with SAC-activated MAD2. SGO2-MAD2 can functionally replace securin and sequesters most separase in securin-knockout cells. Acute loss of securin and SGO2, but not of either protein individually, resulted in separase deregulation associated with premature cohesin cleavage and cytotoxicity. Similar to securin8,9, SGO2 is a competitive inhibitor that uses a pseudo-substrate sequence to block the active site of separase. APC/C-dependent ubiquitylation and action of the AAA-ATPase TRIP13 in conjunction with the MAD2-specific adaptor p31comet liberate separase from SGO2-MAD2 in vitro. The latter mechanism facilitates a considerable degree of sister chromatid separation in securin-knockout cells that lack APC/C activity. Thus, our results identify an unexpected function of SGO2 in mitotically dividing cells and a mechanism of separase regulation that is independent of securin but still supervised by the SAC.
journal_name
Naturejournal_title
Natureauthors
Hellmuth S,Gómez-H L,Pendás AM,Stemmann Odoi
10.1038/s41586-020-2182-3subject
Has Abstractpub_date
2020-04-01 00:00:00pages
536-541issue
7804eissn
0028-0836issn
1476-4687pii
10.1038/s41586-020-2182-3journal_volume
580pub_type
杂志文章相关文献
NATURE文献大全abstract::An optimal search theory, the so-called Lévy-flight foraging hypothesis, predicts that predators should adopt search strategies known as Lévy flights where prey is sparse and distributed unpredictably, but that Brownian movement is sufficiently efficient for locating abundant prey. Empirical studies have generated con...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09116
更新日期:2010-06-24 00:00:00
abstract::To cause diseases in plants, pathogenic microorganisms have evolved mechanisms to deliver proteins directly into plant cells, where they suppress plant defences and facilitate tissue invasion. How plant pathogenic fungi, which cause many of the world's most serious plant diseases, deliver proteins during plant infecti...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04567
更新日期:2006-03-23 00:00:00
abstract::In 1994, two independent groups extracted DNA from several Pleistocene epoch mammoths and noted differences among individual specimens. Subsequently, DNA sequences have been published for a number of extinct species. However, such ancient DNA is often fragmented and damaged, and studies to date have typically focused ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07446
更新日期:2008-11-20 00:00:00
abstract::Since the pioneering work of the Millers it has become clear that most chemical carcinogens require metabolism to reactive electrophiles and then exhibit their carcinogenic potential by reacting chemically with, and modifying, cellular macromolecules. At first modification of proteins was considered most likely to be ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/287244a0
更新日期:1980-09-18 00:00:00
abstract::Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2-20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and the...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12912
更新日期:2014-01-23 00:00:00
abstract::The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA+) cells. These cells also express programmed death l...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature24302
更新日期:2017-11-16 00:00:00
abstract::Comprehensive identification of polymorphisms among individuals within a species is essential both for studying the genetic basis of phenotypic differences and for elucidating the evolutionary history of the species. Large-scale polymorphism surveys have recently been reported for human, mouse and Arabidopsis thaliana...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07670
更新日期:2009-03-19 00:00:00
abstract::Hydrogen peroxide (H2O2) is a major reactive oxygen species in unicellular and multicellular organisms, and is produced extracellularly in response to external stresses and internal cues1-4. H2O2 enters cells through aquaporin membrane proteins and covalently modifies cytoplasmic proteins to regulate signalling and ce...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2032-3
更新日期:2020-02-01 00:00:00
abstract::Naturally occurring peptides with biological actions have in most cases been detected by observing their biological activities in crude extracts and their isolation has been followed using bioassays. As a complement to the classical biological detection systems, we have proposed a chemical detection system based on fr...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/285417a0
更新日期:1980-06-05 00:00:00
abstract::Clouds on Titan result from the condensation of methane and ethane and, as on other planets, are primarily structured by circulation of the atmosphere. At present, cloud activity mainly occurs in the southern (summer) hemisphere, arising near the pole and at mid-latitudes from cumulus updrafts triggered by surface hea...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08014
更新日期:2009-06-04 00:00:00
abstract::Zooxanthellae, endosymbiotic algae of reef-building corals, substantially contribute to the high gross primary production of coral reefs, but corals exude up to half of the carbon assimilated by their zooxanthellae as mucus. Here we show that released coral mucus efficiently traps organic matter from the water column ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature02344
更新日期:2004-03-04 00:00:00
abstract::The global mid-ocean ridge system is the most extensive magmatic system on our planet and is the site of 75 per cent of Earth's volcanism1. The vertical extent of mid-ocean-ridge magmatic systems has been considered to be restricted: even at the ultraslow-spreading Gakkel mid-ocean ridge under the Arctic Ocean, where ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1448-0
更新日期:2019-08-01 00:00:00
abstract::The most severe excursions in the Earth's climatic history are thought to be associated with Proterozoic glaciations. According to the 'Snowball Earth' hypothesis, the Marinoan glaciation, which ended about 635 million years ago, involved global or nearly global ice cover. At the termination of this glacial period, ra...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03176
更新日期:2005-01-13 00:00:00
abstract::The chemical composition of basaltic magma erupted at the Earth's surface is the end product of a complex series of processes, beginning with partial melting and melt extraction from a mantle source and ending with fractional crystallization and crustal assimilation at lower pressures. It has been proposed that studyi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05759
更新日期:2007-05-17 00:00:00
abstract::Evolution of the earliest mammals shows successive episodes of diversification. Lineage-splitting in Mesozoic mammals is coupled with many independent evolutionary experiments and ecological specializations. Classic scenarios of mammalian morphological evolution tend to posit an orderly acquisition of key evolutionary...
journal_title:Nature
pub_type: 历史文章,杂志文章,评审
doi:10.1038/nature06277
更新日期:2007-12-13 00:00:00
abstract::Cutaneous melanoma is a type of cancer with an inherent potential for lymph node colonization, which is generally preceded by neolymphangiogenesis. However, sentinel lymph node removal does not necessarily extend the overall survival of patients with melanoma. Moreover, lymphatic vessels collapse and become dysfunctio...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature22977
更新日期:2017-06-28 00:00:00
abstract::Aberrant neovascularization contributes to diseases such as cancer, blindness and atherosclerosis, and is the consequence of inappropriate angiogenic signalling. Although many regulators of pathogenic angiogenesis have been identified, our understanding of this process is incomplete. Here we explore the transcriptome ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12345
更新日期:2013-07-18 00:00:00
abstract::The development of a eutherian mammal as a male is a consequence of testis formation in the embryo, which is thought to be initiated by a gene on the Y chromosome. In the absence of this gene, ovaries are formed and female characteristics develop. Sex determination therefore hinges on the action of this testis-determi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/348450a0
更新日期:1990-11-29 00:00:00
abstract::Organocatalysis-catalysis mediated by small chiral organic molecules-is a powerful technology for enantioselective synthesis, and has extensive applications in traditional ionic, two-electron-pair reactivity domains. Recently, organocatalysis has been successfully combined with photochemical reactivity to unlock previ...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature25175
更新日期:2018-01-31 00:00:00
abstract::Excitation-contraction coupling in skeletal muscle involves a voltage sensor in the plasma membrane which, in response to depolarization, causes an intracellular calcium-release channel to open. The skeletal isoform of the ryanodine receptor (RyR-1) functions as the Ca2+-release channel and the dihydropyridine recepto...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/380072a0
更新日期:1996-03-07 00:00:00
abstract::Since the origins of agriculture, the scale of human cooperation and societal complexity has dramatically expanded. This fact challenges standard evolutionary explanations of prosociality because well-studied mechanisms of cooperation based on genetic relatedness, reciprocity and partner choice falter as people increa...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature16980
更新日期:2016-02-18 00:00:00
abstract::The DNA polymerase V (pol V) and RecA proteins are essential components of a mutagenic translesion synthesis pathway in Escherichia coli designed to cope with DNA damage. Previously, it has been assumed that RecA binds to the DNA template strand being copied. Here we show, however, that pol-V-catalysed translesion syn...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05042
更新日期:2006-08-24 00:00:00
abstract::For parallel computers to simulate our brains, we must face the fact that human beings have a better claim on the title Homo seriatim than Homo sapiens--we're more consistently serial than wise. ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/330033a0
更新日期:1987-11-05 00:00:00
abstract::Vertical movement of the hip during locomotion causes a loaded backpack to be accelerated with each step, which imposes large peak forces on the wearer. Here we show that using bungee cords to suspend the load from a backpack frame reduces not only its vertical movement, and hence its vertical force on the carrier, bu...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/4441023a
更新日期:2006-12-21 00:00:00
abstract::Three interleukin-1 inhibitors have been purified to homogeneity from medium conditioned by human monocytes. Partial sequence analysis and digestion with N-glycanase indicate that these are glycosylation forms of a single protein. The protein binds to the interleukin-1 receptor but has no interleukin-1-like activity, ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/343336a0
更新日期:1990-01-25 00:00:00
abstract::First recognized as regulators of development in worms and fruitflies, microRNAs are emerging as pivotal modulators of mammalian cardiovascular development and disease. Individual microRNAs modulate the expression of collections of messenger RNA targets that often have related functions, thereby governing complex biol...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature09783
更新日期:2011-01-20 00:00:00
abstract::The direct involvement of the pituitary-adrenal axis in birth has been well established, at least in sheep, and its removal prolongs pregnancy. As part of the process the fetal sheep adrenal grows rapidly during the 10-15 d prepartum and is associated with a large rise in the plasma corticosteroid concentration. This ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/284616a0
更新日期:1980-04-17 00:00:00
abstract::The emission of isoprene from the leaves of forest trees is a fundamental component of biosphere-atmosphere interactions, controlling many aspects of photochemistry in the lower atmosphere. As almost all commercial agriforest species emit high levels of isoprene, proliferation of agriforest plantations has significant...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01312
更新日期:2003-01-16 00:00:00
abstract::S-100 protein, one of the unique proteins found in the nervous system, has recently been discovered unexpectedly in the rat anterior pituitary. Immunocytochemistry reveals that stellate, follicular and folliculostellate cells, and marginal cells of the rat anterior pituitary contain this protein; however, as far as we...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/303711a0
更新日期:1983-06-23 00:00:00
abstract::The single endogenous DBA/2J ectropic provirus segregated concordantly with the dilute (d) coat colour mutation on chromosome 9 in 53/53 DBA/2J-derived recombinant inbred mouse strains and all seven inbred and mutant strains tested that carry the d allele. Analysis of DNA from a spontaneous DBA/2J d revertant (d+2J) s...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/293370a0
更新日期:1981-10-01 00:00:00