The Multiple Roles of Ubiquitylation in Regulating Challenged DNA Replication

  • Sara Villa-Hernández
  • Avelino Bueno
  • Rodrigo BermejoEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1042)


DNA replication is essential for the propagation of life and the development of complex organisms. However, replication is a risky process as it can lead to mutations and chromosomal alterations. Conditions challenging DNA synthesis by replicative polymerases or DNA helix unwinding, generally termed as replication stress, can halt replication fork progression. Stalled replication forks are unstable, and mechanisms exist to protect their integrity, which promote an efficient restart of DNA synthesis and counteract fork collapse characterized by the accumulation of DNA lesions and mutagenic events. DNA replication is a highly regulated process, and several mechanisms control replication timing and integrity both during unperturbed cell cycles and in response to replication stress. Work over the last two decades has revealed that key steps of DNA replication are controlled by conjugation of the small peptide ubiquitin. While ubiquitylation was traditionally linked to protein degradation, the complexity and flexibility of the ubiquitin system in regulating protein function have recently emerged. Here we review the multiple roles exerted by ubiquitin-conjugating enzymes and ubiquitin-specific proteases, as well as readers of ubiquitin chains, in the control of eukaryotic DNA replication and replication-coupled DNA damage tolerance and repair.


DNA replication Replication forks Replication stress DNA damage response DNA repair DNA damage tolerance Ubiquitin Ubiquitin ligases DUBs Cdc48/p97 



We apologize for relevant findings and studies that might have not been discussed due to space limitations. This work was supported by the Ministry of Economy and Competitiveness (BFU2014-52529-R to R.B. and BFU2015-69709-P to A.B.). S.V-H received support from the Spanish Formación de Personal Investigador (FPI) program.


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Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Sara Villa-Hernández
    • 1
  • Avelino Bueno
    • 2
    • 3
  • Rodrigo Bermejo
    • 1
    Email author
  1. 1.Centro de Investigaciones Biológicas (CSIC)MadridSpain
  2. 2.Instituto de Biología Molecular y Celular del Cáncer (USAL/CSIC)SalamancaSpain
  3. 3.Departamento de Microbiología y Genética, Universidad de SalamancaSalamancaSpain

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