Caroline Kisker: DNA Repair
Our DNA is constantly damaged by endogenous and exogenous sources such as reactive oxygen species produced as by-products of oxidative metabolism, or by environmental factors such as UV radiation. Failure to repair these damages leads to tumor formation as observed in the nucleotide repair deficient xeroderma pigmentosum patients. Nucleotide excision repair (NER) recognizes damages such as the carcinogenic pyrimidine dimers induced by UV radiation, benzo[a]pyrene-guanine adducts caused by smoking, as well as guanine-cisplatinum adducts formed during chemotherapy. It is our goal to obtain a general understanding of the sequential process of damage recognition followed by excision of the damage through a combination of structural, microscopic and biochemical studies involving the discrete steps of the NER cascade.
Jung LA, Gebhardt A, Koelmel W, Ade CP, Walz S, Kuper J, von Eyss B, Letschert S, Redel C, d'Artista L, Biankin A, Zender L, Sauer M, Wolf E, Evan G, Kisker C*, Eilers M*, OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors, Oncogene. 2016 Oct 17. doi: 10.1038/onc.2016.354. [Epub ahead of print]
Rohleder F, Huang J, Xue Y, Kuper J, Round A, Seidman M, Wang W, Kisker C, FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks, Nucleic Acids Res. 2016 Apr 20;44(7):3219-32.
Koch SC, Kuper J, Gasteiger KL, Wichlein N, Strasser R, Eisen D, Geiger S, Schneider S, Kisker C*, Carell T.*, Structural insights into the recognition of cisplatin and AAF-dG lesion by Rad14 (XPA). Proc Natl Acad Sci USA. 2015 Jul 7;112(27):8272-7.
Kuper J, Braun C, Elias A, Michels G, Sauer F, Schmitt DR, Poterszman A, Egly JM*, Kisker C*, In TFIIH, XPD helicase is exclusively devoted to DNA repair. PLoS Biol. 2014 Sep 30;12(9):e1001954.
Kuper J, Wolski S, Michels G, Kisker C, Functional and structural studies of the nucleotide excision repair helicase XPD suggest a polarity for DNA. EMBO J. 2012; 31: 494-502.