Multivalent interaction of ESCO2 with the replication machinery is required for sister chromatid cohesion in vertebrates

Dawn Bender, Eulália Maria Lima Da Silva, Jingrong Chen, Annelise Poss, Lauren Gawey, Zane Rulon, Susannah Rankin

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The tethering together of sister chromatids by the cohesin complex ensures their accurate alignment and segregation during cell division. In vertebrates, sister chromatid cohesion requires the activity of the ESCO2 acetyltransferase, which modifies the Smc3 subunit of cohesin. It was shown recently that ESCO2 promotes cohesion through interaction with the MCM replicative helicase. However, ESCO2 does not significantly colocalize with the MCM complex, suggesting there are additional interactions important for ESCO2 function. Here we show that ESCO2 is recruited to replication factories, sites of DNA replication, through interaction with PCNA. We show that ESCO2 contains multiple PCNA-interaction motifs in its N terminus, each of which is essential to its ability to establish cohesion. We propose that multiple PCNA-interaction motifs embedded in a largely flexible and disordered region of the protein underlie the unique ability of ESCO2 to establish cohesion between sister chromatids precisely as they are born during DNA replication.

Original languageEnglish
Pages (from-to)1081-1089
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number2
DOIs
StatePublished - 14 Jan 2020
Externally publishedYes

Keywords

  • Chromosome biology
  • Cohesin
  • DNA replication
  • Sister chromatid cohesion

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