Sumoylation of the DNA polymerase ε by the Smc5/6 complex contributes to DNA replication


Autoři: Xiangzhou Meng aff001;  Lei Wei aff001;  Xiao P. Peng aff001;  Xiaolan Zhao aff001
Působiště autorů: Molecular Biology Department, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America aff001;  Tri-Institutional MD-PhD Program of Weill Cornell Medical School, Rockefeller University, and Sloan-Kettering Cancer Center, New York, New York, United States of America aff002
Vyšlo v časopise: Sumoylation of the DNA polymerase ε by the Smc5/6 complex contributes to DNA replication. PLoS Genet 15(11): e32767. doi:10.1371/journal.pgen.1008426
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008426

Souhrn

DNA polymerase epsilon (Pol ε) is critical for genome duplication, but little is known about how post-translational modification regulates its function. Here we report that the Pol ε catalytic subunit Pol2 in yeast is sumoylated at a single lysine within a catalytic domain insertion uniquely possessed by Pol2 family members. We found that Pol2 sumoylation occurs specifically in S phase and is increased under conditions of replication fork blockade. Analyses of the genetic requirements of this modification indicate that Pol2 sumoylation is associated with replication fork progression and dependent on the Smc5/6 SUMO ligase known to promote DNA synthesis. Consistently, the pol2 sumoylation mutant phenotype suggests impaired replication progression and increased levels of gross chromosomal rearrangements. Our findings thus indicate a direct role for SUMO in Pol2-mediated DNA synthesis and a molecular basis for Smc5/6-mediated regulation of genome stability.

Klíčová slova:

DNA replication – DNA synthesis – Immunoprecipitation – Lysine – Protein domains – SUMOylation – Synthesis phase – Telomeres


Zdroje

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Genetika Reprodukční medicína

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PLOS Genetics


2019 Číslo 11

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