Dr. Björn Schumacher

Institute for Genetics

IGSDHD Faculty


Project proposal: DNA Damage and Aging

Genome Instability has been recognized as causal factor of cancer and recently also as a major contributing factor of aging. A number of skin cancer susceptibility and progeroid (premature aging-like) syndromes are linked to defects in nucleotide excision repair (NER). NER thus provides a highly relevant experimental system to study the role of genome integrity both in cancer and in aging. Using the NER system we recently uncovered a novel link between DNA damage accumulation and the regulation of longevity assurance programs and tumor suppressor mechanisms. We are using the powerful genetic system of C. elegans to identify mechanisms through which the stochastic accumulation of damage impacts aging and genetic pathways of longevity regulation. The conserved NER mechanisms in C. elegans enable us to study the effect of persistent DNA damage in proliferative germ cell compartments as well as in somatic tissues in vivo. Our work aims at the discovery of novel genes functioning in genome integrity and longevity regulation that might be instrumental for the development of preventive therapeutic strategies for age-related pathologies as well as for the treatment of rare genetic progeroid and skin cancer susceptibility syndromes.

References

Reinhardt HC, Schumacher B The p53 network: Cellular and systemic DNA damage responses in aging and cancer Trends Genet. 2012 Jan 19.

Schwer B, Schumacher B, Lombard DB, Xiao C, Kurtev MV, Gao J, Schneider JI, Chai H, Bronson RT, Tsai LH, Deng CX, Alt FW. Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity. Proc Natl Acad Sci U S A. 2010 Nov 22.

Motameny S, Wolters S, Nürnberg P, Schumacher B. Next Generation Sequencing of miRNAs – Strategies, Resources and Methods. Genes. 2010; 1(1):70-84.

Lans H, Marteijn JA, Schumacher B, Hoeijmakers JH, Jansen G, Vermeulen W. Involvement of global genome repair, transcription coupled repair, and chromatin remodeling in UV DNA damage response changes during development. PLoS Genet. 2010 May 6;6:e1000941.

Schumacher B Transcription-blocking DNA damage in aging: a mechanism for hormesis. Bioessays. 2009 Dec;31(12):1347-56.

Garinis GA, Schumacher B Transcription-blocking DNA damage in aging and longevity. Cell Cycle. 2009 Jul 20;8(14).

Garinis GA, Uittenboogaard LM, Stachelscheid H, Fousteri M, van Ijcken W, Breit TM, van Steeg H, Mullenders LHF, van der Horst GTJ, Brüning JC, Niessen CM, Hoeijmakers JHJ and Schumacher B. Persistent transcription-blocking DNA lesions trigger somatic growth attenuation associated with longevity. Nature Cell Biol. 2009 May;11(5):604-15.

Schumacher B, Hoeijmakers JH, Garinis GA. Sealing the gap between nuclear DNA damage and longevity. Mol Cell Endocrinol. 2009 Feb 5;299(1):112-7. Epub 2008 Nov 5.

Schumacher B, van der Pluijm I, Moorhouse MJ, Rasile Robinson A, Suh Y, Breit TM, van Steeg H, Niedernhofer LJ, van Ijcken W, Bartke A, Spindler SR, Hoeijmakers JHJ, van der Horst GTJ and Garinis GA. Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet. 2008 Aug 15;4(8):e1000161.

Greiss S, Schumacher B, Grandien K, Rothblatt J and Gartner A. Transcriptional profiling in C. elegans cep-1/p53 dependent apoptosis as a primordial function of p53 like genes. BMC Genomics. 2008 Jul 15;9(1):334.

Schumacher B, Garinis G, Hoeijmakers J. Age to survive: DNA damage and aging. Trends Genet. 2008 Feb;24(2):77-85.

Garinis G, Patil C, Schumacher B. "The molecular basis of aging": the Boehringer Ingelheim Fonds 95th International Titisee Conference. Mech Ageing Dev. 2007 Jul-Aug;128(7-8):469-75. Schumacher B & Gartner A. Translational regulation of p53 as a potential tumor therapy target. Future Oncology, 2006;2(1):145-153.

Schumacher B, Hanazawa M, Lee M, Nayak S, Volkmann K, Hofmann R, Hengartner M, Schedl T, Gartner A. Translational Repression of C. elegans p53 by GLD-1 regulates DNA damage induced apoptosis. Cell, 11 February 2005; 120: 357-368.

Schumacher B, Schertel C, Wittenburg N, Tuck S, Mitani S, Gartner A, Conradt B, Shaham S. C. elegans ced-13 can promote apoptosis and is induced in response to DNA damage. Cell Death Differ. 2005 Feb;12(2):153-61.

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