Skip to main content
Log in

Sister chromatid resolution: a cohesin releasing network and beyond

  • REVIEW
  • Published:
Chromosoma Aims and scope Submit manuscript

Abstract

When chromosomes start to assemble in mitotic prophase, duplicated chromatids are not discernible within each chromosome. As condensation proceeds, they gradually show up, culminating in two rod-shaped structures apposed along their entire length within a metaphase chromosome. This process, known as sister chromatid resolution, is thought to be a prerequisite for rapid and synchronous separation of sister chromatids in anaphase. From a mechanistic point of view, the resolution process can be dissected into three distinct steps: (1) release of cohesin from chromosome arms; (2) formation of chromatid axes mediated by condensins; and (3) untanglement of inter-sister catenation catalyzed by topoisomerase II (topo II). In this review article, we summarize recent progress in our understanding the molecular mechanisms of sister chromatid resolution with a major focus on its first step, cohesin release. An emerging idea is that this seemingly simple step is regulated by an intricate network of positive and negative factors, including cohesin-binding proteins and mitotic kinases. Interestingly, some key factors responsible for cohesin release in early mitosis also play important roles in controlling cohesin functions during interphase. Finally, we discuss how the step of cohesin release might mechanistically be coordinated with the actions of condensins and topo II.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Andreassen PR, Lacroix FB, Margolis RL (1997) Chromosomes with two intact axial cores are induced by G2 checkpoint override: evidence that DNA decatenation is not required to template the chromosome structure. J Cell Biol 136:29–43

    Article  CAS  PubMed  Google Scholar 

  • Bayliss R, Littlewood T, Stewart M (2000) Structural basis for the interaction between FxFG nucleoporin repeats and importin-beta in nuclear trafficking. Cell 102:99–108

    Article  CAS  PubMed  Google Scholar 

  • Ben-Shahar TR, Heeger S, Lehane C, East P, Flynn H, Skehel M, Uhlmann F (2008) Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion. Science 321:563–566

    Article  CAS  Google Scholar 

  • Bernard P, Schmidt CK, Vaur S, Dheur S, Drogat J, Genier S, Ekwall K, Uhlmann F, Javerzat JP (2008) Cell-cycle regulation of cohesin stability along fission yeast chromosomes. EMBO J 27:111–121

    Article  CAS  PubMed  Google Scholar 

  • Boyarchuk Y, Salic A, Dasso M, Arnaoutov A (2007) Bub1 is essential for assembly of the functional inner centromere. J Cell Biol 176:919–928

    Article  CAS  PubMed  Google Scholar 

  • Coelho PA, Queiroz-Machado J, Carmo AM, Moutinho-Pereira S, Maiato H, Sunkel CE (2008) Dual role of topoisomerase II in centromere resolution and aurora B activity. PLoS Biol 6:e207

    Article  PubMed  Google Scholar 

  • Diaz-Martinez LA, Gimenez-Abian JF, Clarke DJ (2008) Chromosome cohesion—rings, knots, orcs and fellowship. J Cell Sci 121:2107–2114

    Article  CAS  PubMed  Google Scholar 

  • Gandhi R, Gillespie PJ, Hirano T (2006) Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase. Curr Biol 16:2406–2417

    Article  CAS  PubMed  Google Scholar 

  • Gimenez-Abian JF, Sumara I, Hirota T, Hauf S, Gerlich D, de la Torre C, Ellenberg J, Peters JM (2004) Regulation of sister chromatid cohesion between chromosome arms. Curr Biol 14:1187–1193

    Article  CAS  PubMed  Google Scholar 

  • Harrison BD, Hoang ML, Bloom K (2009) Persistent mechanical linkage between sister chromatids throughout anaphase. Chromosoma 118:633–645

    Article  CAS  PubMed  Google Scholar 

  • Hartman T, Stead K, Koshland D, Guacci V (2000) Pds5p is an essential chromosomal protein required for both sister chromatid cohesion and condensation in Saccharomyces cerevisiae. J Cell Biol 151:613–626

    Article  CAS  PubMed  Google Scholar 

  • Hauf S, Roitinger E, Koch B, Dittrich CM, Mechtler K, Peters JM (2005) Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2. PLoS Biol 3:e69

    Article  PubMed  Google Scholar 

  • Hirano T (2005) Condensins: organizing and segregating the genome. Curr Biol 15:R265–275

    Article  CAS  PubMed  Google Scholar 

  • Hirota T, Gerlich D, Koch B, Ellenberg J, Peters JM (2004) Distinct functions of condensin I and II in mitotic chromosome assembly. J Cell Sci 117:6435–6445

    Article  CAS  PubMed  Google Scholar 

  • Hudson DF, Marshall KM, Earnshaw WC (2009) Condensin: architect of mitotic chromosomes. Chromosome Res 17:131–144

    Article  CAS  PubMed  Google Scholar 

  • Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y (2006) Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 441:46–52

    Article  CAS  PubMed  Google Scholar 

  • Kueng S, Hegemann B, Peters BH, Lipp JJ, Schleiffer A, Mechtler K, Peters JM (2006) Wapl controls the dynamic association of cohesin with chromatin. Cell 127:955–967

    Article  CAS  PubMed  Google Scholar 

  • Lengronne A, McIntyre J, Katou Y, Kanoh Y, Hopfner KP, Shirahige K, Uhlmann F (2006) Establishment of sister chromatid cohesion at the S. cerevisiae replication fork. Mol Cell 23:787–799

    Article  CAS  PubMed  Google Scholar 

  • Losada A, Hirano T (2001) Shaping the metaphase chromosome: coordination of cohesion and condensation. Bioessays 23:924–935

    Article  CAS  PubMed  Google Scholar 

  • Losada A, Hirano T (2005) Dynamic molecular linkers of the genome: the first decade of SMC proteins. Genes Dev 19:1269–1287

    Article  CAS  PubMed  Google Scholar 

  • Losada A, Hirano M, Hirano T (1998) Identification of Xenopus SMC protein complexes required for sister chromatid cohesion. Genes Dev 12:1986–1997

    Article  CAS  PubMed  Google Scholar 

  • Losada A, Hirano M, Hirano T (2002) Cohesin release is required for sister chromatid resolution, but not for condensin-mediated compaction, at the onset of mitosis. Genes Dev 16:3004–3016

    Article  CAS  PubMed  Google Scholar 

  • Losada A, Yokochi T, Hirano T (2005) Functional contribution of Pds5 to cohesin-mediated cohesion in human cells and Xenopus egg extracts. J Cell Sci 118:2133–2141

    Article  CAS  PubMed  Google Scholar 

  • Maeshima K, Laemmli UK (2003) A two-step scaffolding model for mitotic chromosome assembly. Dev Cell 4:467–480

    Article  CAS  PubMed  Google Scholar 

  • Marko JF (2008) Micromechanical studies of mitotic chromosomes. Chromosome Res 16:469–497

    Article  CAS  PubMed  Google Scholar 

  • McGuinness BE, Hirota T, Kudo NR, Peters JM, Nasmyth K (2005) Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells. PLoS Biol 3:e86

    Article  PubMed  Google Scholar 

  • Nakajima M, Kumada K, Hatakeyama K, Noda T, Peters JM, Hirota T (2007) The complete removal of cohesin from chromosome arms depends on separase. J Cell Sci 120:4188–4196

    Article  CAS  PubMed  Google Scholar 

  • Nasmyth K, Haering CH (2005) The structure and function of SMC and kleisin complexes. Annu Rev Biochem 74:595–648

    Article  CAS  PubMed  Google Scholar 

  • Neuwald AF, Hirano T (2000) HEAT repeats associated with condensins, cohesins, and other complexes involved in chromosome-related functions. Genome Res 10:1445–1452

    Article  CAS  PubMed  Google Scholar 

  • Panizza S, Tanaka T, Hochwagen A, Eisenhaber F, Nasmyth K (2000) Pds5 cooperates with cohesin in maintaining sister chromatid cohesion. Curr Biol 10:1557–1564

    Article  CAS  PubMed  Google Scholar 

  • Poirier MG, Marko JF (2002) Mitotic chromosomes are chromatin networks without a mechanically contiguous protein scaffold. Proc Natl Acad Sci USA 99:15393–15397

    Article  CAS  PubMed  Google Scholar 

  • Rowland BD, Roig MB, Nishino T, Kurze A, Uluocak P, Mishra A, Beckouet F, Underwood P, Metson J, Imre R et al (2009) Building sister chromatid cohesion: smc3 acetylation counteracts an antiestablishment activity. Mol Cell 33:763–774

    Article  CAS  PubMed  Google Scholar 

  • Shintomi K, Hirano T (2009) Releasing cohesin from chromosome arms in early mitosis: opposing actions of Wapl–Pds5 and Sgo1. Genes Dev 23:2224–2236

    Article  CAS  PubMed  Google Scholar 

  • Sumara I, Vorlaufer E, Stukenberg PT, Kelm O, Redemann N, Nigg EA, Peters JM (2002) The dissociation of cohesin from chromosomes in prophase is regulated by Polo-like kinase. Mol Cell 9:515–525

    Article  CAS  PubMed  Google Scholar 

  • Sutani T, Kawaguchi T, Kanno R, Itoh T, Shirahige K (2009) Budding yeast Wpl1(Rad61)–Pds5 complex counteracts sister chromatid cohesion-establishing reaction. Curr Biol 19:492–497

    Article  CAS  PubMed  Google Scholar 

  • Takahashi TS, Basu A, Bermudez V, Hurwitz J, Walter JC (2008) Cdc7-Drf1 kinase links chromosome cohesion to the initiation of DNA replication in Xenopus egg extracts. Genes Dev 22:1894–1905

    Article  CAS  PubMed  Google Scholar 

  • Tanaka K, Hao Z, Kai M, Okayama H (2001) Establishment and maintenance of sister chromatid cohesion in fission yeast by a unique mechanism. EMBO J 20:5779–5790

    Article  CAS  PubMed  Google Scholar 

  • Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H (2006) PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell 10:575–585

    Article  CAS  PubMed  Google Scholar 

  • Terret ME, Sherwood R, Rahman S, Qin J, Jallepalli PV (2009) Cohesin acetylation speeds the replication fork. Nature 462:231–234

    Article  CAS  PubMed  Google Scholar 

  • Toyoda Y, Yanagida M (2006) Coordinated requirements of human topo II and cohesin for metaphase centromere alignment under Mad2-dependent spindle checkpoint surveillance. Mol Biol Cell 17:2287–2302

    Article  CAS  PubMed  Google Scholar 

  • Verni F, Gandhi R, Goldberg ML, Gatti M (2000) Genetic and molecular analysis of wings apart-like (wapl), a gene controlling heterochromatin organization in Drosophila melanogaster. Genetics 154:1693–1710

    CAS  PubMed  Google Scholar 

  • Waizenegger IC, Hauf S, Meinke A, Peters JM (2000) Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase. Cell 103:399–410

    Article  CAS  PubMed  Google Scholar 

  • You Z, Chahwan C, Bailis J, Hunter T, Russell P (2005) ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol Cell Biol 25:5363–5379

    Article  CAS  PubMed  Google Scholar 

  • Yu HG, Koshland D (2005) Chromosome morphogenesis: condensin-dependent cohesin removal during meiosis. Cell 123:397–407

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank members of the Hirano laboratory for critically reading the manuscript. Work in the authors’ laboratory is supported by Grant-in-Aid for Specially Promoted Research (20002010) (to T.H.). K.S. is a RIKEN Special Postdoctoral Researcher and was supported by an Incentive Research Grant from RIKEN.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tatsuya Hirano.

Additional information

Communicated by: E. Nigg

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shintomi, K., Hirano, T. Sister chromatid resolution: a cohesin releasing network and beyond. Chromosoma 119, 459–467 (2010). https://doi.org/10.1007/s00412-010-0271-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00412-010-0271-z

Keywords

Navigation