Research Groups

Telomeres and Genome Integrity

Cancer progression and organismal ageing are complex biological processes that share common molecular mechanisms. Although the exact nature of their relationship is currently unclear, telomere biology has emerged as a key link between these two processes.
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  • Michael Chang Visit
    Position

    Group Leader of the Laboratory of Telomeres and Genome Integrity

    Research fields

    Telomeres, telomerase, DNA replication, DNA recombination, DNA damage, yeast

    Postdoctoral Fellows
    Daniele Novarina
    PhD Students
    Paula van Mourik
  • Telomeres, the physical ends of eukaryotic chromosomes, help distinguish natural chromosome ends from DNA breaks in need of repair. Dysfunctional telomeres result in DNA damage checkpoint activation and cell cycle arrest. Telomeres progressively shorten due to incomplete DNA replication and nucleolytic degradation. When telomeres are critically shortened, cells can no longer divide, reaching a state known as replicative senescence. Shortening is counteracted by telomerase, the specialized reverse transcriptase that elongates telomeres. However, most human somatic cells do not express sufficient telomerase to prevent telomere shortening, which has been proposed as one reason why human individuals age. Replicative senescence functions as a barrier to tumorigenesis since cancer cells need to maintain their telomeres to continue proliferating. Most cancer cells overcome this barrier via the activation of telomerase. However, ~15% of human cancers use telomerase-independent mechanisms termed Alternative Lengthening of Telomeres (ALT). The goal of Michael Chang’s lab is to understand the process of senescence and to characterize how cells maintain their telomeres, both by telomerase and telomerase-independent mechanisms.
    • Claussin C, Porubský D, Spierings DCJ, Halsema N, Rentas S,  Guryev V,  Lansdorp PM,  Chang M Co  -corresponding author. (2017) Genome-wide mapping of sister chromatid exchange events in single yeast cells using Strand-seq Elife
    • Stinus S, Paeschke K, Chang M (2017)Telomerase regulation by the Pif1 helicase: a length-dependent effect? Current Genetics.  
    • Strecker J, Stinus S, Caballero MP, Szilard RK, Chang M, Durocher D.(2017) A sharp Pif1-dependent threshold separates DNA double-strand breaks from critically short telomeres. Elife.  
    • Hemelaar SR, van der Laan KJ, Hinterding SR, Koot MV, Ellermann E, Perona-Martinez FP, Roig D, Hommelet S, Novarina D, Takahashi H, Chang M, and Schirhagl R. (2017) Generally Applicable Transformation Protocols for Fluorescent Nanodiamond Internalization into Cells. Scientific Reports.  
    • Cabrera M, Novarina D, Rempel IL, Veenhoff LM, and Chang M. (2017) A simple microfluidic platform to study age-dependent protein abundance and localization changes in Saccharomyces cerevisiae. Microbial Cell.
    • Novarina D, Mavrova SN, Janssens GE, Rempel IL, Veenhoff LM, Chang M. (2017) Increased genome instability is not accompanied by sensitivity to DNA damaging agents in aged yeast cells. DNA repair.
    • Claussin C, Chang M. (2016) Multiple Rad52-mediated homology-directed repair mechanisms are required to prevent telomere attrition-induced senescence in Saccharomyces cerevisiae. PLoS Genetics.
    • van Mourik PM, de Jong J, Agpalo D, Claussin C, Rothstein R, and Chang M. (2016) Recombination-mediated telomere maintenance in Saccharomyces cerevisiae is not dependent on the Shu complex. PLOS ONE.
    • Claussin C, Chang M. (2015) The many facets of homologous recombination at telomeres. Microbial Cell.
    • Gupta A, Sharma S, Reichenbach P, Marjavaara L, Nilsson AK, Lingner J, Chabes A, Rothstein R, Chang M. (2013) Telomere length homeostasis responds to changes in intracellular dNTP pools. Genetics.
    • Poschke H, Dees M, Chang M, Amberkar S, Kaderali L, Rothstein R, Luke B. (2012) Rif2 promotes a telomere fold-back structure through Rpd3L recruitment in budding yeast. PLoS Genetics.
    • Chang M. (2012) Long telomeres: too much of a good thing. Biomolecular Concepts.
    • Chang M, Rothstein R. (2011) Rif1/2 and Tel1 function in separate pathways during replicative senescence. Cell Cycle.
    • Chang M, Dittmar JC, Rothstein R. (2011) Long Telomeres are Preferentially Extended During Recombination-Mediated Telomere Maintenance. Nature Structural & Molecular Biology.
    • Chang M, Luke B, Kraft C, Li Z, Peter M, Lingner J, Rothstein R. (2009) Telomerase is essential to alleviate pif1-induced replication stress at telomeres. Genetics.
    • Chang M, Lingner J. (2008) Tel2 finally tells one story. Science.
    • Chang M, Arneric M, Lingner J. (2007) Telomerase repeat addition processivity is increased at critically short telomeres in a Tel1-dependent manner in Saccharomyces cerevisiae. Genes & Development.
    • Wu L, Bachrati CZ, Ou J, Xu C, Yin J, Chang M, Wang W, Li L, Brown GW, Hickson ID. (2006) BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. PNAS.
    • Chang M, Parsons AB, Sheikh BH, Boone C, Brown GW. (2006) Genomic approaches for identifying DNA damage response pathways in S. cerevisiae. Methods in Enzymology.
    • Chang M, Bellaoui M, Zhang C, Desai R, Morozov P, Delgado-Cruzata L, Rothstein R, Freyer GA, Boone C, Brown GW. (2005) RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex. the EMBO Journal.
    • Suter B, Tong A, Chang M, Yu L, Brown GW, Boone C, Rine J. (2004) The origin recognition complex links replication, sister chromatid cohesion and transcriptional silencing in Saccharomyces cerevisiae. Genetics.
    • Tong AH, et al. (2004) Global mapping of the yeast genetic interaction network. Science.
    • Mayer ML, Pot I, Chang M, Xu H, Aneliunas V, Kwok T, Newitt R, Aebersold R, Boone C, Brown GW, Hieter P. (2004) Identification of protein complexes required for efficient sister chromatid cohesion. Molecular Biology of the Cell.
    • Mohammed Bellaoui, Michael Chang, Jiongwen Ou, Hong Xu, Charles Boone, Grant W. Brown. (2003) Elg1 forms an alternative RFC complex important for DNA replication and genome integrity. The EMBO journal.
    • Chang M, Bellaoui M, Boone C, Brown GW. (2002) A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage. PNAS.
    • Baetz K, Moffat J, Haynes J, Chang M, Andrews B. (2001) Transcriptional coregulation by the cell integrity mitogen-activated protein kinase Slt2 and the cell cycle regulator Swi4. Molecular and cellular biology.
  • Margarita Cabrera
    Senior postdoctoral fellow 2014-2015

    Current position:
    Ramon y Cajal Fellow
    Oxidative Stress and Cell Cycle Research Group
    Universitat Pompeu Fabra (Barcelona, Spain)

    Clémence Claussin
    PhD 2012-2017

    Current position:
    Postdoctoral Fellow
    Lab of Dr. Iestyn Whitehouse Sloan Kettering Institute (New York, NY, USA)

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