Cleavage of Cohesin by the CD Clan Protease Separin Triggers Anaphase in Yeast

doi:10.1016/S0092-8674(00)00130-6

Home
/
Papers
/
Cleavage of Cohesin by the CD Clan Protease Separin Triggers Anaphase in Yeast

Journal Article•DOI•

Cleavage of Cohesin by the CD Clan Protease Separin Triggers Anaphase in Yeast

Frank Uhlmann¹, Dominik Wernic², Poupart Marc-Andre², Eugene V. Koonin, Kim Nasmyth¹ - Show less +1 more•Institutions (2)

Research Institute of Molecular Pathology¹, Boehringer Ingelheim²

27 Oct 2000-Cell (Cell)-Vol. 103, Iss: 3, pp 375-386

TL;DR: It is shown here that separin is a cysteine protease related to caspases that alone can cleave Sccl in vitro and depends on a conserved protein called separin for sister chromatid separation.

read less

About: This article is published in Cell.The article was published on 2000-10-27 and is currently open access. It has received 867 citations till now. The article focuses on the topics: Separase & Cohesin.

...read moreread less

Citations

PDF

Open Access

More filters

Journal Article•DOI•

Mitotic kinases as regulators of cell division and its checkpoints

[...]

Erich A. Nigg¹•Institutions (1)

Max Planck Society¹

01 Jan 2001-Nature Reviews Molecular Cell Biology

TL;DR: An overview of the many mitotic kinases that regulate cell division and the fidelity of chromosome transmission is given.

...read moreread less

Abstract: Mitosis and cytokinesis are undoubtedly the most spectacular parts of the cell cycle. Errors in the choreography of these processes can lead to aneuploidy or genetic instability, fostering cell death or disease. Here, I give an overview of the many mitotic kinases that regulate cell division and the fidelity of chromosome transmission.

...read moreread less

1,540 citations

Journal Article•DOI•

Ubiquitin ligases: cell-cycle control and cancer

[...]

Keiichi I. Nakayama¹, Keiko Nakayama²•Institutions (2)

Kyushu University¹, Tohoku University²

01 May 2006-Nature Reviews Cancer

TL;DR: A better understanding of the ubiquitylation machinery will provide new insights into the regulatory biology of cell-cycle transitions and the development of anti-cancer drugs.

...read moreread less

Abstract: A driving force of the cell cycle is the activation of cyclin-dependent kinases (CDKs), the activities of which are controlled by the ubiquitin-mediated proteolysis of key regulators such as cyclins and CDK inhibitors. Two ubiquitin ligases, the SKP1-CUL1-F-box-protein (SCF) complex and the anaphase-promoting complex/cyclosome (APC/C), are responsible for the specific ubiquitylation of many of these regulators. Deregulation of the proteolytic system might result in uncontrolled proliferation, genomic instability and cancer. Cumulative clinical evidence shows alterations in the ubiquitylation of cell-cycle regulators in the aetiology of many human malignancies. A better understanding of the ubiquitylation machinery will provide new insights into the regulatory biology of cell-cycle transitions and the development of anti-cancer drugs.

...read moreread less

1,365 citations

Journal Article•DOI•

Cohesin mediates transcriptional insulation by CCCTC-binding factor

[...]

Kerstin S. Wendt¹, Keisuke Yoshida², Takehiko Itoh³, Masashige Bando², Birgit Koch¹, Erika Schirghuber¹, Shuichi Tsutsumi⁴, Genta Nagae⁴, Ko Ishihara⁵, Tsuyoshi Mishiro⁵, Kazuhide Yahata⁶, Fumio Imamoto⁶, Hiroyuki Aburatani⁴, Mitsuyoshi Nakao⁵, Naoko Imamoto, Kazuhiro Maeshima, Katsuhiko Shirahige², Jan-Michael Peters¹ - Show less +14 more•Institutions (6)

Research Institute of Molecular Pathology¹, Tokyo Institute of Technology², Mitsubishi Research Institute³, University of Tokyo⁴, Kumamoto University⁵, Osaka University⁶

14 Feb 2008-Nature

TL;DR: It is proposed that cohesin functions as a transcriptional insulator, and it is speculated that subtle deficiencies in this function contribute to ‘cohesinopathies’ such as Cornelia de Lange syndrome.

...read moreread less

Abstract: Cohesin complexes mediate sister-chromatid cohesion in dividing cells but may also contribute to gene regulation in postmitotic cells. How cohesin regulates gene expression is not known. Here we describe cohesin-binding sites in the human genome and show that most of these are associated with the CCCTC-binding factor (CTCF), a zinc-finger protein required for transcriptional insulation. CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 (insulin-like growth factor 2) locus. This role of cohesin seems to be independent of its role in cohesion. We propose that cohesin functions as a transcriptional insulator, and speculate that subtle deficiencies in this function contribute to 'cohesinopathies' such as Cornelia de Lange syndrome.

...read moreread less

1,164 citations

Journal Article•DOI•

The anaphase-promoting complex: proteolysis in mitosis and beyond.

[...]

Jan-Michael Peters¹•Institutions (1)

Research Institute of Molecular Pathology¹

01 May 2002-Molecular Cell

TL;DR: Key events in mitosis such as sister chromatid separation and subsequent inactivation of cyclin-dependent kinase 1 are regulated by ubiquitin- dependent proteolysis, mediated by the anaphase-promoting complex.

...read moreread less

949 citations

Journal Article•DOI•

Cohesin: Its Roles and Mechanisms

[...]

Kim Nasmyth¹, Christian H. Haering•Institutions (1)

University of Oxford¹

17 Nov 2009-Annual Review of Genetics

TL;DR: Evidence suggests that cohesin acts as a novel topological device that traps chromosomal DNA within a large tripartite ring formed by its core subunits.

...read moreread less

Abstract: The cohesin complex is a major constituent of interphase and mitotic chromosomes. Apart from its role in mediating sister chromatid cohesion, it is also important for DNA double-strand-break repair and transcriptional control. The functions of cohesin are regulated by phosphorylation, acetylation, ATP hydrolysis, and site-specific proteolysis. Recent evidence suggests that cohesin acts as a novel topological device that traps chromosomal DNA within a large tripartite ring formed by its core subunits.

...read moreread less

917 citations

Cites background from "Cleavage of Cohesin by the CD Clan ..."

...Cleavage of α-kleisin at TEV sites either at a mutated separase site (187) or elsewhere within its central domain (44, 130) does indeed have this effect....
[...]
...There is overwhelming evidence in yeast that sister chromatid disjunction is triggered by cleavage of cohesin’s α-kleisin subunit Scc1 by separase (178, 185, 187)....
[...]
...The second takes place shortly before the onset of anaphase, when all remaining cohesin (mainly at centromeres but also on arms) dissociates due to cleavage of its α-kleisin subunit by separase (53, 89, 118, 185, 187, 202)....
[...]
...Separase activity must be highly regulated and is inhibited for much of the cell cycle through its association with a specific inhibitory chaperone known as securin (187)....
[...]
...The second phase involves separase, a highly conserved CD clan thiol protease, whose cleavage of Scc1 removes cohesin from chromosomes and triggers (at least in yeast) sister chromatid disjunction (130, 185, 187, 194)....
[...]

1
2
3
4
…
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174

Collapse

References

PDF

Open Access

More filters

Journal Article•DOI•

Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

[...]

Stephen F. Altschul¹, Thomas L. Madden, Alejandro A. Schäffer¹, Jinghui Zhang, Zheng Zhang², Webb Miller², David J. Lipman - Show less +3 more•Institutions (2)

National Institutes of Health¹, Pennsylvania State University²

01 Sep 1997-Nucleic Acids Research

TL;DR: A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original.

...read moreread less

Abstract: The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSIBLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.

...read moreread less

70,111 citations

"Cleavage of Cohesin by the CD Clan ..." refers methods in this paper

...This protocol yielded 25 mg of purified Scc1 or purified BLAST program (Altschul et al., 1997)....
[...]

Journal Article•DOI•

MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures

[...]

P. J. Kraulis

01 Oct 1991-Journal of Applied Crystallography

TL;DR: The MOLSCRIPT program as discussed by the authors produces plots of protein structures using several different kinds of representations, including simple wire models, ball-and-stick models, CPK models and text labels.

...read moreread less

Abstract: The MOLSCRIPT program produces plots of protein structures using several different kinds of representations. Schematic drawings, simple wire models, ball-and-stick models, CPK models and text labels can be mixed freely. The schematic drawings are shaded to improve the illusion of three dimensionality. A number of parameters affecting various aspects of the objects drawn can be changed by the user. The output from the program is in PostScript format.

...read moreread less

13,971 citations

Additional excerpts

...MOLSCRIPT: a program to produce both de-S....
[...]
...The figure was drawn with MOLSCRIPT (Kraulis, 1991)....
[...]

Journal Article•DOI•

Protein secondary structure prediction based on position-specific scoring matrices

[...]

David T. Jones¹•Institutions (1)

University of Warwick¹

17 Sep 1999-Journal of Molecular Biology

TL;DR: A two-stage neural network has been used to predict protein secondary structure based on the position specific scoring matrices generated by PSI-BLAST and achieved an average Q3 score of between 76.5% to 78.3% depending on the precise definition of observed secondary structure used, which is the highest published score for any method to date.

...read moreread less

5,512 citations

"Cleavage of Cohesin by the CD Clan ..." refers methods in this paper

...The reaction was stopped by adding SDS-PAGE 1994) and PSIPRED (Jones, 1999) programs.loading buffer, and aliquots were analyzed by SDS-PAGE and Western blotting against the Flag epitope....
[...]

Journal Article•DOI•

Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis

[...]

Donald W. Nicholson¹, Ambereen Ali¹, Nancy A. Thornberry¹, John P. Vaillancourt¹, C K Ding¹, Michel Gallant¹, Yves Gareau¹, Patrick R. Griffin¹, Marc Labelle¹, Yuri Lazebnik² - Show less +6 more•Institutions (2)

Merck & Co.¹, Cold Spring Harbor Laboratory²

06 Jul 1995-Nature

TL;DR: A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death.

...read moreread less

Abstract: The protease responsible for the cleavage of poly(ADP-ribose) polymerase and necessary for apoptosis has been purified and characterized. This enzyme, named apopain, is composed of two subunits of relative molecular mass (M(r)) 17K and 12K that are derived from a common proenzyme identified as CPP32. This proenzyme is related to interleukin-1 beta-converting enzyme (ICE) and CED-3, the product of a gene required for programmed cell death in Caenorhabditis elegans. A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death.

...read moreread less

4,096 citations

"Cleavage of Cohesin by the CD Clan ..." refers background in this paper

...…Scc1 cleavage site peptide, synthesized as inhibitors against Esp1. nome databases of several new members of this family peptide based inhibitors (Nicholson et al., 1995; Faleiro et al., 1997) that form a covalent bond with their activehave highlighted the most conserved amino acid residues…...
[...]

Journal Article•DOI•

New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites.

[...]

R D Gietz¹, A Sugino¹•Institutions (1)

National Institutes of Health¹

30 Dec 1988-Gene

TL;DR: The production of new alleles of the LEU2, URA3 and TRP1 genes of Saccharomyces cerevisiae by in vitro mutagenesis is described and a unique series of yeast-Escherichia coli shuttle vectors derived from the plasmid pUC19 are constructed.

...read moreread less

2,860 citations

"Cleavage of Cohesin by the CD Clan ..." refers methods in this paper

...The TEV protease coding FBX1000, and FBX100, containing 1 M and 100 mM NaCl, respectively. sequence was cloned into YIp204 (Gietz and Sugino, 1988) under Beads were then resuspended in a total volume of 100 ml FBX100 control of the GAL promoter....
[...]
...…and Purification of Esp1 from Yeast Cells The Esp1 coding sequence was cloned under control of the GAL A biotinylated peptidyl chloromethyl ketone (cmk) and a peptidyl (2,4,6-trimethylbenzoyloxy)methyl ketone (acyloxymethyl ketone,promoter into the yeast vector YIp204 (Gietz and Sugino, 1988)....
[...]
...Peptide Based Covalent Inhibitors for Esp1-Dependent Scc1 CleavageOverexpression and Purification of Esp1 from Yeast Cells The Esp1 coding sequence was cloned under control of the GAL A biotinylated peptidyl chloromethyl ketone (cmk) and a peptidyl (2,4,6-trimethylbenzoyloxy)methyl ketone (acyloxymethyl ketone,promoter into the yeast vector YIp204 (Gietz and Sugino, 1988)....
[...]