PCNA controls establishment of sister chromatid cohesion during S phase.
Accurate segregation of the genetic material during cell division requires that sister chromatids are kept together by cohesion proteins until anaphase, when the chromatids become separated and distributed to the two daughter cells. Studies in yeast revealed that chromatid cohesion is essential for viability and is triggered by the conserved protein Eco1 (Ctf7). Cohesion must be established already in S phase in order to tie up sister chromatids instantly after replication, but how this crucial timing is achieved remains enigmatic. Here, we report that in yeast and humans Eco1 is directly physically coupled to the replication protein PCNA, a ring-shaped cofactor of DNA polymerases. Binding to PCNA is crucial, as yeast Eco1 mutants deficient in Eco1-PCNA interaction are defective in cohesion and inviable. Our study thus indicates that PCNA, a central matchmaker for replication-linked functions, is also crucially involved in the establishment of cohesion in S phase.
Moldovan
George-Lucian
GL
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Pfander
Boris
B
Jentsch
Stefan
S
D000123:Acetyltransferases / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D002842:Chromatids / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism; D023902:Chromosome Pairing; D017124:Conserved Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D000123:Acetyltransferases; C118076:ECO1 protein, S cerevisiae; C500785:ESCO2 protein, human