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Oncogenomics: Jacqueline Jacobs

Telomere Damage and Cancer

Research interest

Natural chromosome ends are capped by specialized nucleoprotein structures called telomeres. Telomeres are essential for the maintenance of genome integrity by protecting natural chromosome ends from being seen and treated as broken DNA ends. Telomeres consist of tandem TTAGGG DNA repeat sequences bound by the 'shelterin' complex of telomere-specific proteins that control the length and end-protection function of telomeres. Chromosome ends can lose telomere protection when telomeres become critically short as a consequence of multiple rounds of cell division and when the activity of shelterin components is lost.

When telomeres become dysfunctional they limit the replicative lifespan of a cell by activating a DNA damage response that forces it into a senescent state or to undergo cell death (apoptosis). While these both contribute to the aging process, they also act as a mechanism to inhibit cancer development by limiting the outgrowth of incipient cancer cells. However, if the cell escapes senescence or death and divides, misplaced DNA repair at chromosome ends causes end-to-end chromosomal fusions that can lead to extensive genome instability and ultimately to cancer.

The aim of our work is to understand the molecular mechanisms that underlie these responses to telomere dysfunction and that have critical consequences for cancer development and aging. To do this, we take both unbiased and candidate-driven approaches, alongside in-depth mechanistic studies, particularly focused on identifying what precise DNA damage signaling responses and processing activities act at telomeres and how these are regulated.

We are utilizing genetic screens and proteomics-based approaches to identify proteins and post-translational modifications with critical roles in the cellular response to unprotected telomeres. We use well-controllable models such as the fast and reversible temperature-dependent inactivation of the telomere-capping protein TRF2, which allows us to investigate both immediate and late events associated with the activation of DNA damage responses at telomeres. These models also allow us to address how DNA damage responses are inhibited or terminated. Through subsequent functional studies on the newly identified factors and pathways, we aim to generate a comprehensive understanding of the mechanisms underlying telomere-dependent control of cancer development and aging.


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Inge de Krijger

Ph.D. student


After finishing my bachelor in Molecular Life Science I studied at the University of Vermont for one semester and continued with my Masters in Molecular Life Science at the Radboud University in Nijmegen. During my master I did two research internships, starting at the Department of Pathology at the Radboud UMC Nijmegen where I worked on microRNAs. My second internship was performed at the Signal Transduction Laboratory of Julian Downward in the London Research Institute, working on PI3K signaling. In november I started in the lab of Jacqueline Jacobs focusing on the role of methylation in the telomere damage response.

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Yalcin, Zeliha.jpg

Zeliha Yalcin

Ph.D. student


I am Zeliha and I did a Master in Biomolecular Sciences at the Vrije Universiteit (VU) in Amsterdam. My first internship was at the Netherlands Cancer Institute (NKI) in the group of Huib Ovaa, where I characterized and inhibited deubiquitinating enzymes in Trypanosoma brucei. My second internship was at the Leiden University Medical Center in the group of Marjolein Kikkert, where I studied the function of conserved cysteines in Equine arteritis virus non-structural protein 2.

In December 2012, I joined the lab of Jacqueline Jacobs as a PhD student, where I work on ubiquitination in the telomere damage response.

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Serrat, Judit

Judit Serrat



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Cerutti, Aurora

Aurora Cerutti

Postdoctoral fellow


I obtained my PhD in Fabrizio d'Adda di Fagagna's lab, at IFOM in Milan, where I worked on oncogene-induced DNA damage and DNA replication stress, with particular focus on telomeres. Supported by EMBO short term fellowship, I spent few months at Genomic Vision, Paris, to learn DNA Molecular Combing, a cutting-edge technique to study DNA replication dynamics. I have been involved in various international collaborations related to replication stress at whole genome level and at telomeres. In Jacqueline Jacobs' lab, my aim is to better dissect the pathways and factors involved in telomere maintenance by focusing on telomere damage regulation, as well as telomere replication stress.

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Research updates View All Updates

  • PhD fellowship from Boehringer Ingelheim Fonds

    Inge de Krijger was awarded a highly competitive PhD fellowship from Boehringer Ingelheim Fonds. Starting October 1st, 2013 this fellowship will support 2 years of her PhD studies on the role of methylation in the telomere damage response.

  • We are looking for highly motivated and talented postdocs to join us. Please check our vacancies web page or directly email Jacqueline Jacobs with your motivation letter, CV, list of publications and contact details of at least 2 referees.

Key publications View All Publications

  • DNA-damage response and repair activities at uncapped telomeres depend on RNF8

    Nat Cell Biol. 2011; 13: 1139-45

    Peuscher MH, Jacobs JJ.

    link to PubMed
  • MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5' end resection.

    Nature. 2015 May 28

    Boersma V, Moatti N, Segura-Bayona S, Peuscher MH, van der Torre J, Wevers BA, Orthwein A, Durocher D, Jacobs JJ.

    Link to PubMed

Recent publications View All Publications

  • PARP1 Links CHD2-Mediated Chromatin Expansion and H3.3 Deposition to DNA Repair by Non-homologous End-Joining.

    Mol Cell. 2016 Feb 18

    Luijsterburg MS, de Krijger I, Wiegant WW, Shah RG, Smeenk G, de Groot AJ, Pines A, Vertegaal AC, Jacobs JJ, Shah GM, van Attikum H.

    link to PubMed
  • Loss of telomere protection: consequences and opportunities

    Front Oncol. 2013; 3: 88

    Jacobs, JJ

    link to PubMed


  • E-mail

  • Telephone Number

    +31 20 512 2015


'Research for the benefit of cancer patients'

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