YEAST 2017

28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

August 27 – September 1, 2017
Prague, Czech Republic


Paper ID: 272

DDK-mediated regulation of the deSUMOylating enzyme Ulp2 facilitates early steps of DNA replication 

Psakhye Ivan, Castellucci Federica, Branzei Dana

IFOM, the FIRC Institute of Molecular Oncology (Italy)

ABSTRACT

Dbf4-dependent kinase Cdc7 (DDK) is crucial for chromosome replication initiation, by activating the replicative helicase, MCM. Other means of DDK-dependent control of replication are less understood. Here we uncover that the budding yeast deSUMOylating enzyme, Ulp2, is a DDK substrate that binds to replication origins and promotes early steps of DNA replication. In DDK mutants and phosphodeficient Ulp2 variants, Ulp2 chromatin binding is deregulated, being less concentrated at origins and more diffused along chromosomes. Furthermore, in ulp2 mutants, origin firing-derived replication intermediates and BrdU incorporation efficiency are decreased. Notably, the replication initiation defects of ulp2 cells were rescued by removing the SUMO-targeted ubiquitin ligase (STUbL), Slx5/8. We propose that DDK regulates Ulp2 distribution and concentration at firing origins to ensure a critical mass of replisome factors poised for replication upon MCM activation.

Keywords:
Dbf4-dependent kinase, DNA replication, replisome factors
Presented as:
  Oral presentation [S8-2] in S8 DNA replication, mutation and repair

Institute of Microbiology

YEAST 2017
28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

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