DNA Repair and Epigenomics
Table of Contents
Overview
Optimal function of the cellular DNA repair machinery plays a critical role in preserving genomic integrity. Defective or impaired DNA repair increases genomic instability and contributes to malignant transformation.
Genetic and epigenetic repair gene modifications are both contributing to tumor development. Promoter methylation of specific DNA repair genes is an important example how epigenetically silenced targets affect tumor development as well as tumor therapy. There is increasing evidence that
- more repair genes are regulated by epigenetic mechanisms,
- specific repair enzymes are closely cooperating with the DNA methylation-/demethylation machinery, and
- DNA damaging agents can affect epigenetic patterns within the cell nucleus.
Present Research Projects
to comprehensively screen human DNA repair genes for promoter hypermethylation and identify new repair genes not yet known to be silenced by methylation
to elucidate interactions of DNA damage and repair mechanisms with epigenetic gene regulation, especially DNA methylation
to identify DNA damage-induced (e.g. by ionizing radiation) changes in the DNA methylation patterns
to identify functional deficiencies in DNA damage response and repair and to elucidate their impact on individual cancer risk, radiosensitivity, therapy outcome and prognosis
to develop and validate sensitive methods and biomarkers for the characterization of individual DNA repair deficiencies and identification of high risk individuals.
Selected References
Popanda O, Seibold P, Nikolov I, Oakes CC, Burwinkel B, Hausmann S, Flesch-Janys D, Plass C, Chang-Claude J, Schmezer P. Germline variants of base excision repair genes and breast cancer: A polymorphism in DNA polymerase gamma modifies gene expression and breast cancer risk. Int J Cancer. 2012 [Epub ahead of print]
Chaisaingmongkol J, Popanda O, Warta R, Dyckhoff G, Herpel E, Geiselhart L, Claus R, Lasitschka F, Campos B, Oakes CC, Bermejo JL, Herold-Mende C, Plass C, Schmezer P. Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma. Oncogene 2012 [Epub ahead of print]
Abbasi R, Efferth T, Kuhmann C, Opatz T, Hao X, Popanda O, Schmezer P. The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells. Toxicol Appl Pharmacol 2012, 15; 259(3): 302-10.
Campos B, Warta R, Chaisaingmongkol J, Geiselhart L, Popanda O, Hartmann C, von Deimling A, Unterberg A, Plass C, Schmezer P, Herold-Mende C. Epigenetically mediated down-regulation of the differentiation-promoting chaperon protein CRABP2 in astrocytic gliomas. Int J Cancer 2012, 131(8): 1963-8.
Kuhmann C, Weichenhan D, Rehli M, Plass C, Schmezer P, Popanda O DNA methylation changes in cells regrowing after fractioned ionizing radiation. Radiother Oncol. 2011, 101: 16-21
Mayer C, Popanda O, Greve B, Fritz E, Illig T, Eckardt-Schupp F, Gomolka M, Benner A, Schmezer P. A radiation-induced gene expression signature as a tool to predict acute radiotherapy-induced adverse side effects. Cancer Lett. 2011, 302: 20-28.
Seibold P, Hein R, Schmezer P, Hall P, Liu J, Dahmen N, Flesch-Janys D, Popanda O, Chang-Claude J. Polymorphisms in oxidative stress-related genes and postmenopausal breast cancer risk, Int. J. Cancer 2011, 129: 1467-76.
Goeppert B, Schmezer P, Dutruel C, Oakes C, Renner M, Breinig M, Warth A, Vogel MN, Mittelbronn M, Mehrabi A, Gdynia G, Penzel R, Longerich T, Breuhahn K, Popanda O, Plass C, Schirmacher P, Kern MA. Downregulation of tumor suppressor A kinase anchor protein 12 in human hepatocarcinogenesis by epigenetic mechanisms, Hepatology 2010, 52: 2023-33.
Abbasi R, Ramroth H, Becher H, Dietz A, Schmezer P, Popanda O. Laryngeal cancer risk associated with smoking and alcohol consumption is modified by genetic polymorphisms in ERCC5, ERCC6, and RAD23B but not by polymorphisms in five other nucleotide excision repair genes. Int. J. Cancer 2009, 125:1431-1439
Chang-Claude J, Ambrosone CB, Lilla C, Kropp S, Helmbold I, von Fournier D, Haase W, Sautter-Bihl ML, Wenz F, Schmezer P, Popanda O. Genetic polymorphisms in DNA repair and damage response genes and late normal tissue complications of radiotherapy for breast cancer. British Journal of Cancer 2009, 100:1680-1686
Greve B, Dreffke K, Rickinger A, Könemann S, Fritz E, Eckardt-Schupp F, Amler S, Sauerland C, Braselmann H, Sauter W, Illig T, Schmezer P, Gomolka M, Willich N, Bölling T. Multicentric investigation of ionising radiation-induced cell death as a predictive parameter of individual radiosensitivity. Apoptosis 2009, 14:226-235
Popanda O, Marquardt JU, Chang-Claude J, Schmezer P. Genetic variation in normal tissue toxicity induced by ionizing radiation. Mutation Research / Fundamental and Molecular Mechanisms of Mutagenesis 2009, 667:58-69
Schmezer P, Plass C. Epigenetic aspects in carcinomas of the head and neck. HNO 2008, 56:594-602
Wischermann K, Popp S, Moshir S, Scharfetter-Kochanek K, Wlaschek M, de Gruijl F, Hartschuh W, Greinert R, Volkmer B, Faust A, Rapp A, Schmezer P, Boukamp P. UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes. Oncogene 2008, 27:4269-80
Woelfelschneider A, Popanda O, Lilla C, Linseisen J, Mayer C, Celebi O, Debus J, Bartsch H, Chang-Claude J, Schmezer P. A distinct ERCC1 haplotype is associated with mRNA expression levels in prostate cancer patients. Carcinogenesis 2008, 29:1758-64
Sangrajrang S, Schmezer P, Burkholder I, Waas P, Boffetta P, Brennan P, Bartsch H, Wiangnon S, Popanda O. Polymorphisms in three base excision repair genes and breast cancer risk in Thai women. Breast Cancer Res Treat 2008, 111:279-88
