4.8 Article

Rtt107 Is a Multi-functional Scaffold Supporting Replication Progression with Partner SUMO and Ubiquitin Ligases

期刊

MOLECULAR CELL
卷 60, 期 2, 页码 268-279

出版社

CELL PRESS
DOI: 10.1016/j.molcel.2015.08.023

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资金

  1. US National Institutes of Health [GM080670]
  2. American Cancer Society [RSG-12-013-01-CCG]
  3. Leukemia and Lymphoma Society Scholar Award
  4. Pathway to Independence Award from the National Institutes of Health [4R00GM08137804]
  5. Italian Association for Cancer Research [AIRC IG 14171]
  6. Fondazione Telethon [GGP12160]
  7. European Research Council [REPSUBREP 242928]
  8. Fondazione Italiana per la Ricerca sul Cancro (FIRC) fellowship

向作者/读者索取更多资源

Elucidating the individual and collaborative functions of genome maintenance factors is critical for understanding how genome duplication is achieved. Here, we investigate a conserved scaffold in budding yeast, Rtt107, and its three partners: a SUMOE3 complex, a ubiquitin E3 complex, and Slx4. Biochemical and genetic findings show that Rtt107 interacts separately with these partners and contributes to their individual functions, including a role in replisome sumoylation. We also provide evidence that Rtt107 associates with replisome components, and both itself and its associated E3s are important for replicating regions far from initiation sites. Corroborating these results, replication defects due to Rtt107 loss and genotoxic sensitivities in mutants of Rtt107 and its associated E3s are rescued by increasing replication initiation events through mutating two master repressors of late origins, Mrc1 and Mec1. These findings suggest that Rtt107 functions as a multi-functional platform to support replication progression with its partner E3 enzymes.

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