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Spartan deficiency causes genomic instability and progeroid phenotypes

Author

Listed:
  • Reeja S. Maskey

    (Mayo Clinic)

  • Myoung Shin Kim

    (Mayo Clinic)

  • Darren J. Baker

    (Mayo Clinic)

  • Bennett Childs

    (Mayo Clinic)

  • Liviu A. Malureanu

    (Mayo Clinic)

  • Karthik B. Jeganathan

    (Mayo Clinic)

  • Yuka Machida

    (Mayo Clinic)

  • Jan M. van Deursen

    (Mayo Clinic)

  • Yuichi J. Machida

    (Mayo Clinic
    Mayo Clinic)

Abstract

Spartan (also known as DVC1 and C1orf124) is a PCNA-interacting protein implicated in translesion synthesis, a DNA damage tolerance process that allows the DNA replication machinery to replicate past nucleotide lesions. However, the physiological relevance of Spartan has not been established. Here we report that Spartan insufficiency in mice causes chromosomal instability, cellular senescence and early onset of age-related phenotypes. Whereas complete loss of Spartan causes early embryonic lethality, hypomorphic mice with low amounts of Spartan are viable. These mice are growth retarded and develop cataracts, lordokyphosis and cachexia at a young age. Cre-mediated depletion of Spartan from conditional knockout mouse embryonic fibroblasts results in impaired lesion bypass, incomplete DNA replication, formation of micronuclei and chromatin bridges and eventually cell death. These data demonstrate that Spartan plays a key role in maintaining structural and numerical chromosome integrity and suggest a link between Spartan insufficiency and progeria.

Suggested Citation

  • Reeja S. Maskey & Myoung Shin Kim & Darren J. Baker & Bennett Childs & Liviu A. Malureanu & Karthik B. Jeganathan & Yuka Machida & Jan M. van Deursen & Yuichi J. Machida, 2014. "Spartan deficiency causes genomic instability and progeroid phenotypes," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6744
    DOI: 10.1038/ncomms6744
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    Cited by:

    1. Pedro Weickert & Hao-Yi Li & Maximilian J. Götz & Sophie Dürauer & Denitsa Yaneva & Shubo Zhao & Jacqueline Cordes & Aleida C. Acampora & Ignasi Forne & Axel Imhof & Julian Stingele, 2023. "SPRTN patient variants cause global-genome DNA-protein crosslink repair defects," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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