Recruitment, loading, and activation of the Smc5–Smc6 SUMO ligase

  • Martina Oravcová
  • Michael N. Boddy


Duplication of the genome poses one of the most significant threats to genetic integrity, cellular fitness, and organismal health. Therefore, numerous mechanisms have evolved that maintain replication fork stability in the face of DNA damage and allow faithful genome duplication. The fission yeast BRCT-domain-containing protein Brc1, and its budding yeast orthologue Rtt107, has emerged as a “hub” factor that integrates multiple replication fork protection mechanisms. Notably, the cofactors and pathways through which Brc1, Rtt107, and their human orthologue (PTIP) act have appeared largely distinct. This either represents true evolutionary functional divergence, or perhaps an incomplete genetic and biochemical analysis of each protein. In this regard, we recently showed that like Rtt107, Brc1 supports key functions of the Smc5–Smc6 complex, including its recruitment into DNA repair foci, chromatin association, and SUMO ligase activity. Furthermore, fission yeast cells lacking the Nse5–Nse6 genome stability factor were found to exhibit defects in Smc5–Smc6 function, similar to but more severe than those in cells lacking Brc1. Here, we place these findings in context with the known functions of Brc1, Rtt107, and Smc5–Smc6, present data suggesting a role for acetylation in Smc5–Smc6 chromatin loading, and discuss wider implications for genome stability.


Brc1 Smc5 Smc6 SUMO Rad18 Nse5 Nse6 PTIP Rtt107 Replication stress 



This study was funded by NIH Grants GM068608 and GM081840 awarded to M.N.B.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Molecular MedicineThe Scripps Research InstituteLa JollaUSA

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