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  • Review Article
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MEN and SIN: what's the difference?

Nature Reviews Molecular Cell Biology volume 2, pages 815–826 (2001)Cite this article

Key Points

  • A signalling network known as the mitotic exit network (MEN) in S. cerevisiae and the septation initiation network (SIN) in S. pombe, although conserved, seem to regulate different cell-cycle transitions in the two yeasts. MEN regulates the inactivation of mitotic CDKs at the end of mitosis, whereas SIN controls cytokinesis after mitotic CDK inactivation.

  • But, although these two pathways seem different at first glance, studies are beginning to indicate that the pathways, their regulation and their outputs might not actually be that different. Based on this, we propose that MEN and SIN have similar functions in budding and fission yeast - that is, to both downregulate mitotic CDKs and promote cytokinesis.

  • Therefore, to understand how the cell ensures that the exit from mitosis and cytokinesis occur only at the end of each cell cycle, it will crucial to identify all the signals that control and regulate the MEN and SIN.

  • There is also evidence for homologues of these pathways in higher eukaryotes. Further work might not only shed light on how exit from mitosis and cytokinesis are regulated in higher eukaryotes but also explain some of the mechanisms that lead to aneuploidy, which is often associated with cancerous transformation.

Abstract

A conserved signalling cascade — termed the mitotic-exit network in budding yeast and the septation-initiation network in fission yeast — controls key events during exit from mitosis and cytokinesis. Although the components of these signalling networks are highly conserved between the two yeasts, the outputs seem quite different. How, then, do these two pathways function, and how are they regulated?

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Figure 1: Cdc14 and clp1/flp1 control mitotic CDK activity.
Figure 2: MEN and SIN components — a model for their function in the pathways and signals that regulate them.
Figure 3: Localization of MEN components during the cell cycle.
Figure 4: Localization of SIN components during the cell cycle.

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Acknowledgements

We are grateful to D. McCollum and V. Simanis for communicating results before publication. We thank members of the Amon lab for comments on the manuscript and apologize to our colleagues whose work we could not include due to space limitations.

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Authors and Affiliations

  1. Center for Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, E17-233, 40 Ames Street, Cambridge, 02139, Massachusetts, USA

    Allison J. Bardin & Angelika Amon

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  1. Allison J. Bardin
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Correspondence to Angelika Amon.

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DATABASES

Locuslink:

CDC2

CDC14A

CDC14B

Fnk/Prk

GAPCENA

LATS1

Plk

Polo

Sak

Snk

warts

 Saccharomyces Genome Database:

Bfa1

Byr4

Bub2

Cdc5

Cdc14

Cdc15

Cdc20

Cdh1/Hct1

Clb1

Clb2

Clb3

Clb4

Clb5

Clb6

Cln1

Cln2

Cln3

Cyk1

Dbf2

Esp1

Iqg1

Lte1

Mad2

Mob1

Net1

Nud1

Pds1

Sic1

Swi5

Tem1

Glossary

MITOTIC SPINDLE

An array of microtubules that forms during mitosis to which chromosomes attach and by which chromosomes are segregated to separate daughter cells.

CENTROSOME

The higher eukaryotic equivalent of the spindle-pole body, the centrosome nucleates microtubules, including those that will form the mitotic spindle. It contains two barrel-shaped structures known as centrioles.

CHROMOSOME DECONDENSATION

On entry into mitosis, chromosomes become compacted or 'condensed'. This is especially apparent in fission yeast and higher eukaryotes. During exit from mitosis, this process is reversed and chromosomes become less compacted — a process known as decondensation.

SPINDLE ELONGATION (ANAPHASE B)

After the chromosomes have been pulled to centrosomes, the mitotic spindle lengthens (and in budding yeast, pushes into the growing daughter cell), thereby allowing further separation of the chromosomes.

UBIQUITIN LIGASE

An enzyme which, together with a ubiquitin-conjugating enzyme, attaches ubiquitin peptides to a substrate protein.

26S PROTEASOME

A multi-subunit protease that degrades poly-ubiquitylated proteins.

COHESIN

A protein complex that tethers sister chromatids together from the time they are created (during DNA replication) until cohesin cleavage at the onset of anaphase.

GTPASE-ACTIVATING PROTEIN (GAP)

A protein that inhibits GTPases by increasing their intrinsic ability to hydrolyse GTP, which allows for shorter time in the active, GTP-bound state.

GUANINE-NUCLEOTIDE EXCHANGE FACTOR (GEF)

A protein that activates GTPases by facilitating the exchange of GDP for GTP, thereby allowing for shorter time in the inactive, GDP-bound state.

POLO KINASE

A family of related kinases defined by a conserved region known as the polo box. They are thought to have several roles in the cell, including an important role in centrosome duplication.

SECURIN

(Pds1 in budding yeast, cut2 in fission yeast.) Securin is responsible for keeping separase inactive until metaphase, at which point securin is degraded, thereby liberating separase which, in turn, cleaves the cohesins.

SEPARASE

(Esp1 in budding yeast, cut1 in fission yeast.) A protease that cleaves the cohesin subunit Scc1/Mcd1/Rad21 at two specific sites. Cleavage of these sites by separase allows sister chromatids to separate, leading to the onset of anaphase.

SISTER CHROMATIDS

Chromosomes that have been duplicated during S phase. Sister chromatids are held together by cohesins until metaphase.

KINETOCHORE

A proteinaceous structure that mediates attachment of the chromosomes to microtubules.

MEDIAL RING

A structure in fission yeast, containing F-actin and numerous other proteins, which marks the eventual site of the division septum.

1,3-β-GLUCAN SYNTHASE

An enzyme that makes 1,3-β-glucan, a sugar polymer that is a structural component of the division septum in fission yeast.

F-ACTIN

Filamentous actin. Contraction of filamentous actin is thought to have an important role in cytokinesis.

RAB FAMILY

A conserved family of GTPases whose members are involved in endocytic and exocytic vesicle transport.

MIDBODY

A region of dense matrix material visible in higher eukaryotic cells by electron microscopy. The midbody remains between two daughter cells after the cleavage furrow has contracted.

CLEAVAGE FURROW

A region of the cell membrane in higher eukaryotic cells that ingresses; thought to be a result of contraction of actin and myosin rings.

CENTRIOLE

A cylindrical array of microtubules, two of which are found in the centre of centrosomes and are responsible for nucleation of microtubules.

ACTOMYOSIN AND SEPTIN DYNAMICS

Actomyosin and septin dynamics refers to the contraction of actin, myosin, and septin rings, which is concurrent with cytokinesis in eukaryotic cells.

ANEUPLOIDY

An abnormal number of chromosomes caused by their inaccurate segregation during cell division.

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Bardin, A., Amon, A. MEN and SIN: what's the difference?. Nat Rev Mol Cell Biol 2, 815–826 (2001). https://doi.org/10.1038/35099020

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