Human Scc4 is required for cohesin binding to chromatin, sister-chromatid cohesion, and mitotic progression

Curr Biol. 2006 May 9;16(9):863-74. doi: 10.1016/j.cub.2006.03.049.


Background: Sister-chromatid cohesion depends on the cohesin complex whose association with chromatin is mediated by Scc2 and Scc4 in budding yeast. Both cohesin and Scc2 have been conserved from yeast to humans, but no Scc4 orthologs have been identified. Mutation of Scc2 orthologs causes defects in cohesion, transcription, and development, resulting in Cornelia de Lange syndrome in humans.

Results: We have identified a family of tetratricopeptide repeat proteins that share weak sequence similarities with yeast Scc4. This family includes MAU-2, which is required for development of the nervous system in Caenorhabditis elegans. We show that the human member of this family is associated with Scc2, is bound to chromatin from telophase until prophase, and is required for association of cohesin with chromatin during interphase. Cells lacking Scc4 lose sister-chromatid cohesion precociously and arrest in prometaphase. Mitotic chromosomes in Scc4-depleted cells lack cohesin, even though the cohesin-protecting proteins Sgo1 and Bub1 are normally enriched at centromeres and separase does not seem to be active.

Conclusion: Our data indicate that human Scc4 is required for the association of cohesin with chromatin, which is a prerequisite for the establishment of sister-chromatid cohesion and for chromosome biorientation in mitosis. The proteinaceous machinery that is required for loading of cohesin onto chromatin is therefore conserved from yeast to humans. The finding that Caenorhabditis elegans MAU-2 is an ortholog of Scc4 further supports the notion that the Scc2-Scc4 complex is required for developmental processes in metazoans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle Proteins / physiology
  • Centromere / physiology
  • Chromatids / physiology*
  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / analysis
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / immunology
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomal Proteins, Non-Histone / physiology*
  • HeLa Cells
  • Humans
  • Interphase / physiology
  • Mice
  • Mitosis / physiology*
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Prometaphase / physiology
  • Protein Kinases / physiology
  • Protein-Serine-Threonine Kinases
  • Rats
  • Saccharomyces cerevisiae Proteins / chemistry
  • Sequence Alignment
  • Xenopus
  • Xenopus Proteins / genetics
  • Xenopus Proteins / immunology


  • Antibodies
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Nuclear Proteins
  • SCC4 protein, S cerevisiae
  • SGO1 protein, human
  • Saccharomyces cerevisiae Proteins
  • Scc2 protein, Xenopus
  • Scc4 protein, human
  • Xenopus Proteins
  • cohesins
  • Protein Kinases
  • BUB1 protein, human
  • Bub1 protein, mouse
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases

Associated data

  • GENBANK/AB254826
  • GENBANK/AB254827
  • GENBANK/AB254828
  • GENBANK/AB254829