Schärer, Orlando D. - Stony Brook University

个人简介

MSc. ETH Zürich, Switzerland, 1991 Ph.D. Harvard University, Cambridge, 1996 Postdoctoral, Erasmus University, Rotterdam, Netherlands 1996-1999

研究领域

Our research program is concerned with the mechanisms of DNA repair in higher eukaryotes and the relationship of these processes to carcinogenesis and anti-tumor therapy, focusing on two main questions: 1) What are the molecular mechanisms by which DNA repair pathways prevent carcinogenesis and 2) How might we selectively inhibit DNA repair pathways in tumor cells to counteract resistance to treatment with agents such as cisplatin or nitrogen mustards. Our work combines organic chemistry, biochemistry and structural, molecular and cellular biology to address these questions in the context of nucleotide excision repair and interstrand crosslink repair.

近期论文

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Guillemette S, Branagan A, Peng M, Dhruva A, Schärer OD, Cantor SB (2014) FANCJ localization by mismatch repair is vital to maintain genomic integrity after UV irradiation. Cancer Res 74, 932-944. Schärer OD (2013) Nucleotide Excision Repair in Eukaryotes. Cold Spring Harb Perspect Biol 5, a012609. Clauson C, Schärer OD, Niedernhofer LJ (2013) DNA Interstrand Crosslink Repair. Cold Spring Harb Perspect Biol 5, a012732. Wickramaratne S, Mukherjee S, Villalta P, Schärer OD, Tretyakova N (2013) Synthesis of Site-specific DNA-Protein Crosslinks that Mimic N7-Guanine Lesions via a Reductive Amination Strategy. Bioconj Chem 24, 1496-1506. Bogliolo M, Schuster B, Stoepker C, Derkunt B, Su Y, Raams A, Trujillo JP, Minguillón J, Ramírez MJ, Pujol R, Casado JA, Baños R, Rio P, Knies K, Zúñiga S, Benítez J, Bueren JA, Jaspers NGJ, Schärer OD, Winter JP, Schindler D, Surrallés J (2013) Mutations in ERCC4, encoding the DNA repair endonuclease XPF, cause Fanconi anemia. Am J Hum Genet 92, 800-806. Yeo J-E, Khoo A, Fagbemi AF, Schärer OD (2012) The efficiencies of damage recognition and excision correlate with duplex destabilization induced by acetylaminofluorene adducts in human nucleotide excision repair. Chem Res Tox 25, 2462-2468. Enoiu M, Ho TV, Long DT, Walter JC, Schärer OD (2012) Construction of plasmids containing site-specific DNA interstrand crosslinks for biochemical and cell biological studies. Methods Mol Biol 920, 203-219. Enoiu M, Jiricny J, Schärer OD (2012) Repair of cisplatin-induced DNA interstrand crosslinks by a replication-independent pathway involving transcription-coupled repair and translesion polymerases. Nucleic Acids Res 40, 8953-8964. Schärer OD (2012) Alkylguanine transferase-like proteins: brokers dealing with alkylated DNA bases (Preview), Mol Cell 47, 3-4. Su Y, Orelli B, Madireddy A, Niedernhofer LJ, Schärer OD (2012) Multiple domains of ERCC1-XPF contribute to DNA binding in nucleotide excision repair J Biol Chem 287, 21846-21855. Hentschel S, Alzeer J, Angelov T, Schärer OD, Luedtke NW (2012) Synthesis of DNA interstrand crosslinks using a photocaged nucleobase. Angew Chem 51, 3466-3469. Sidorenko V, Yeo JE, Bonala R, Johnson F, Schärer OD*, Grollman AP* (2012) Resistance to global-genome nucleotide excision repair explains the high mutagenicity and persistence of aristolactam-DNA adducts. Nucleic Acids Res 40, 2494-2505. *Co-corresponding authors Fu YV, Yardimci H, Long DT, Ho TV, Guainazzi A, Bermudez VP, Hurwitz J, van Oijen A, Schärer OD, Walter JC (2011) Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase. Cell 146, 931-941. Fagbemi AF, Orelli B, Schärer OD (2011) Regulation of the endonuclease activities of ERCC1-XPF and XPG in nucleotide excision repair (Invited Review). DNA Repair 10, 722-729. Ho TV, Guainazzi A, Derkunt SB, Enoiu M, Schärer OD (2011) Structure-dependent translesion synthesis of major groove DNA interstrand crosslinks. Nucleic Acids Res 39, 7455-7464. Guainazzi A, Schärer OD (2010) Using synthetic compounds to study DNA interstrand crosslink repair (Invited review). Cell Mol Life Sci 67, 3683-3697. Guainazzi A, Campbell AJ, Angelov T, Simmerling C, Schärer OD (2010) Synthesis and molecular modeling of a nitrogen mustard DNA interstrand crosslink. Chem Eur J 16, 12100-12103. Ho TV, Schärer OD (2010) Translesion synthesis in the repair of DNA interstrand crosslinks (Invited Review for special issue – DNA interstrand crosslink repair). Environ Mol Mutagen 51, 552-566. Ahmad A, Enzlin JH, Wijgers N, Raams A, Appledoorn E, Theil AE, Hoeijmakers JHJ, Vermeulen V, Jaspers NGJ, Schärer OD*, Niedernhofer LJ* (2010) Aberrant sub-cellular localization of DNA repair protein XPF: the molecular basis for extracutaneous symptoms in xeroderma pigmentosum. PLoS Genet 6, e1000871. *Co-corresponding authors Orelli B, McClendon BT, Tsodikov, OV, Ellenberger T, Niedernhofer LJ, Schärer OD (2010) The interaction between ERCC1 and XPA is required for nucleotide excision repair, but not other DNA repair pathways. J Biol Chem 285, 3705-3712. Knipscheer P, Räschle M, Smorgorzewska A, Enoiu M, Ho TV, Schärer OD, Elledge SJ, Walter JC (2009) The Fanconi anemia pathway promotes replication-dependent DNA interstrand crosslink repair. Science 326, 1698-1691. (Highlighted in: Moldovan GL, D’Andrea AD (2009) FancD2 Hurdles the DNA Interstrand Crosslink. Cell 139, 1222-1224) Staresincic L, Fagbemi AF, Enzlin JH, Gourdin AM, Wijgers N, Dunand-Sauthier I, Giglia-Mari G, Clarkson SG, Vermeulen W, Schärer OD (2009) Coordination of dual incision and repair synthesis in human nucleotide excision repair. EMBO J 28, 1111-1120. Angelov T, Guainazzi A, Schärer OD (2009) Generation of DNA interstrand crosslinks by postsynthetic reductive amination. Org Lett 11, 611-614. Räschle M, Knipsheer P, Enoiu M, Angelov T, Sun J, Griffith JD, Ellenberger T, Schärer OD, Walter JC (2008) Mechanism of replication-coupled DNA interstrand cross-link repair. Cell 134, 969-980.