David Scicchitano

The research in my laboratory primarily involves the study of interactions of chemical and physical agents with DNA, and the processing of the resulting damage by cells. To that end, we have been examining the removal of chemical adducts from discrete regions of the genome. This is being done in an effort to characterize a phenomenon known as DNA repair heterogeneity that is typified by the preferential removal of DNA damage from active genetic loci. The implications of biases in DNA repair are vast: Certain segments of the chromosome might be more susceptible to mutagenesis than other domains, making them hot spots for the induction of a variety of detrimental biological outcomes including tumorigenesis and cell death.

A second area of ongoing research involves investigating the effect of site-specific DNA damage on transcription by a variety of RNA polymerases. We use oligonucleotides containing polycyclic aromatic hydrocarbons, an important class of chemical carcinogens, for these studies. We have shown that some of these adducts impede transcription elongation; furthermore, the degree of inhibition is dependent upon the stereochemical configuration of the DNA lesion.

Molecular and Cell Biology I and II, and part of Principles of Biology I

Doctoral Mentor: Anthony E. Pegg; Department of Physiology; The Milton S. Hershey Medical Center; The Pennsylvania State University

Postdoctoral Mentor: Philip C. Hanawalt; Department of Biological Sciences; Stanford University

Professional Experience: Research Scientist; American Health Foundation

American Association for the Advancement of Science, American Association for Cancer Research

Date of these PubMed search results: March 24 2020
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1. The "Real" Chechen Man: Conceptions of Religion, Nature, and Gender and the Persecution of Sexual Minorities in Postwar Chechnya.
   J Homosex (2019 Dec 18) PMID: 31850836
   Scicchitano D
2. O(6)-methylguanine-induced transcriptional mutagenesis reduces p53 tumor-suppressor function.
   Proc Natl Acad Sci U S A (2018 May 1) PMC5939098 free full-text archive
   Ezerskyte M, Paredes JA, Malvezzi S, Burns JA, Margison GP, Olsson M, Scicchitano DA, Dreij K
3. Genetic instability associated with loop or stem-loop structures within transcription units can be independent of nucleotide excision repair.
   Nucleic Acids Res (2018 Apr 20) PMC5909459 free full-text archive
   Burns JA, Chowdhury MA, Cartularo L, Berens C, Scicchitano DA
4. The Nonbulky DNA Lesions Spiroiminodihydantoin and 5-Guanidinohydantoin Significantly Block Human RNA Polymerase II Elongation in Vitro.
   Biochemistry (2017 Jun 20) PMC5872833 free full-text archive
   Kolbanovskiy M, Chowdhury MA, Nadkarni A, Broyde S, Geacintov NE, Scicchitano DA, Shafirovich V
5. Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription.
   J Biol Chem (2016 Jan 8) PMC4705403 free full-text archive
   Nadkarni A, Burns JA, Gandolfi A, Chowdhury MA, Cartularo L, Berens C, Geacintov NE, Scicchitano DA
6. O6-methylguanine induces altered proteins at the level of transcription in human cells.
   Nucleic Acids Res (2010 Dec) PMC3001077 free full-text archive
   Burns JA, Dreij K, Cartularo L, Scicchitano DA
7. Benzo[a]pyrene diol epoxide stimulates an inflammatory response in normal human lung fibroblasts through a p53 and JNK mediated pathway.
   Carcinogenesis (2010 Jun) PMC2878364 free full-text archive
   Dreij K, Rhrissorrakrai K, Gunsalus KC, Geacintov NE, Scicchitano DA
8. Transcription elongation past O6-methylguanine by human RNA polymerase II and bacteriophage T7 RNA polymerase.
   Nucleic Acids Res (2008 Nov) PMC2582612 free full-text archive
   Dimitri A, Burns JA, Broyde S, Scicchitano DA
9. Transcription of DNA containing the 5-guanidino-4-nitroimidazole lesion by human RNA polymerase II and bacteriophage T7 RNA polymerase.
   DNA Repair (Amst) (2008 Aug 2) PMC2572817 free full-text archive
   Dimitri A, Jia L, Shafirovich V, Geacintov NE, Broyde S, Scicchitano DA
10. Transcription processing at 1,N2-ethenoguanine by human RNA polymerase II and bacteriophage T7 RNA polymerase.
    J Mol Biol (2008 Jan 11) PMC2262288 free full-text archive
    Dimitri A, Goodenough AK, Guengerich FP, Broyde S, Scicchitano DA
11. Increased flexibility enhances misincorporation: temperature effects on nucleotide incorporation opposite a bulky carcinogen-DNA adduct by a Y-family DNA polymerase.
    J Biol Chem (2007 Jan 12) PMID: 17090533
    Perlow‑Poehnelt RA, Likhterov I, Wang L, Scicchitano DA, Geacintov NE, Broyde S
12. Transcription past DNA adducts derived from polycyclic aromatic hydrocarbons.
    Mutat Res (2005 Sep 4) PMID: 15922365
    Scicchitano DA
13. Transcription and DNA adducts: what happens when the message gets cut off?
    DNA Repair (Amst) (2004 Dec 2) PMID: 15474416
    Scicchitano DA, Olesnicky EC, Dimitri A
14. The spacious active site of a Y-family DNA polymerase facilitates promiscuous nucleotide incorporation opposite a bulky carcinogen-DNA adduct: elucidating the structure-function relationship through experimental and computational approaches.
    J Biol Chem (2004 Aug 27) PMID: 15210693
    Perlow‑Poehnelt RA, Likhterov I, Scicchitano DA, Geacintov NE, Broyde S
15. Human RNA polymerase II is partially blocked by DNA adducts derived from tumorigenic benzo[c]phenanthrene diol epoxides: relating biological consequences to conformational preferences.
    Nucleic Acids Res (2003 Oct 15) PMC219463 free full-text archive
    Schinecker TM, Perlow RA, Broyde S, Geacintov NE, Scicchitano DA
16. Construction and purification of site-specifically modified DNA templates for transcription assays.
    Nucleic Acids Res (2003 Apr 1) PMC152825 free full-text archive
    Perlow RA, Schinecker TM, Kim SJ, Geacintov NE, Scicchitano DA
17. Base excision repair and nucleotide excision repair contribute to the removal of N-methylpurines from active genes.
    DNA Repair (Amst) (2002 Aug 6) PMID: 12509290
    Plosky B, Samson L, Engelward BP, Gold B, Schlaen B, Millas T, Magnotti M, Schor J, Scicchitano DA
18. DNA adducts from a tumorigenic metabolite of benzo[a]pyrene block human RNA polymerase II elongation in a sequence- and stereochemistry-dependent manner.
    J Mol Biol (2002 Aug 2) PMID: 12139931
    Perlow RA, Kolbanovskii A, Hingerty BE, Geacintov NE, Broyde S, Scicchitano DA
19. [Reconversion after Hartmann's procedure. Our experience].
    Ann Ital Chir (1998 Jan-Feb) PMID: 11995043
    Benedetti M, Marchesi R, Zanardi A, Pastorelli A, Scicchitano D, Castagnoli L, Pandolfi U, Tinozzi S
20. Bacteriophage T7 RNA polymerase transcription elongation is inhibited by site-specific, stereospecific benzo[c]phenanthrene diol epoxide DNA lesions.
    Biochemistry (2001 May 1) PMID: 11318642
    Roth RB, Amin S, Geacintov NE, Scicchitano DA
21. [Inflammatory pseudotumor of the lung. Diagnostic-therapeutic effectiveness of its radical resection].
    Minerva Chir (2000 Nov) PMID: 11265156
    Rizzo S, Marchesi R, Ronchi V, Scicchitano D, Luinetti O, Pandolfi U
22. Transcription and DNA damage: a link to a kink.
    Environ Health Perspect (1997 Feb) PMC1470299 free full-text archive
    Scicchitano DA, Mellon I
23. Functional nucleotide excision repair is required for the preferential removal of N-ethylpurines from the transcribed strand of the dihydrofolate reductase gene of Chinese hamster ovary cells.
    Mol Cell Biol (1997 Feb) PMC231781 free full-text archive
    Sitaram A, Plitas G, Wang W, Scicchitano DA
24. Incorrect base insertion and prematurely terminated transcripts during T7 RNA polymerase transcription elongation past benzo[a]pyrenediol epoxide-modified DNA.
    J Mol Biol (1996 Nov 29) PMID: 8951371
    Choi DJ, Roth RB, Liu T, Geacintov NE, Scicchitano DA
25. 3-Methyladenine and 7-methylguanine exhibit no preferential removal from the transcribed strand of the dihydrofolate reductase gene in Chinese hamster ovary B11 cells.
    Biochemistry (1995 Feb 7) PMID: 7849040
    Wang W, Sitaram A, Scicchitano DA
26. Site-specific benzo[a]pyrene diol epoxide-DNA adducts inhibit transcription elongation by bacteriophage T7 RNA polymerase.
    Biochemistry (1994 Jan 25) PMID: 8292606
    Choi DJ, Marino‑Alessandri DJ, Geacintov NE, Scicchitano DA
27. Intragenomic repair heterogeneity of DNA damage.
    Environ Health Perspect (1992 Nov) PMC1519617 free full-text archive
    Scicchitano DA, Hanawalt PC
28. Two expressed human genes sustain slightly more DNA damage after alkylating agent treatment than an inactive gene.
    Mutat Res (1991 Nov) PMID: 1719396
    Bartlett JD, Scicchitano DA, Robison SH
29. Lack of sequence-specific removal of N-methylpurines from cellular DNA.
    Mutat Res (1990 Nov-Dec) PMID: 2233810
    Scicchitano DA, Hanawalt PC
30. Measurements of genomic and gene-specific DNA repair of alkylation damage in cultured human T-lymphocytes.
    Basic Life Sci (1990) PMID: 2126430
    Hartshorn JN, Scicchitano DA, Robison SH
31. Repair of N-methylpurines in specific DNA sequences in Chinese hamster ovary cells: absence of strand specificity in the dihydrofolate reductase gene.
    Proc Natl Acad Sci U S A (1989 May) PMC287062 free full-text archive
    Scicchitano DA, Hanawalt PC
32. Use of oligodeoxynucleotides containing O6-alkylguanine for the assay of O6-alkylguanine-DNA-alkyltransferase activity.
    Cancer Res (1988 Mar 1) PMID: 3342398
    Dolan ME, Scicchitano D, Pegg AE
33. Inhibition of O6-alkylguanine-DNA-alkyltransferase by metals.
    Mutat Res (1987 Nov) PMID: 3683440
    Scicchitano DA, Pegg AE
34. Specificity of O6-alkylguanine-DNA alkyltransferase.
    IARC Sci Publ (1987) PMID: 3679391
    Pegg AE, Scicchitano D, Morimoto K, Dolan ME
35. Repair of oligodeoxynucleotides containing O6-methylguanine by O6-alkylguanine-DNA-alkyltransferase.
    Carcinogenesis (1986 Aug) PMID: 3731392
    Scicchitano D, Jones RA, Kuzmich S, Gaffney B, Lasko DD, Essigmann JM, Pegg AE
36. Studies of the repair of O6-alkylguanine and O4-alkylthymine in DNA by alkyltransferases from mammalian cells and bacteria.
    Environ Health Perspect (1985 Oct) PMC1568696 free full-text archive
    Pegg AE, Dolan ME, Scicchitano D, Morimoto K
37. Repair of O6-propylguanine and O6-butylguanine in DNA by O6-alkylguanine-DNA alkyltransferases from rat liver and E. coli.
    Carcinogenesis (1985 Jul) PMID: 3893782
    Morimoto K, Dolan ME, Scicchitano D, Pegg AE
38. Comparison of the rates of repair of O6-alkylguanines in DNA by rat liver and bacterial O6-alkylguanine-DNA alkyltransferase.
    Cancer Res (1984 Sep) PMID: 6378375
    Pegg AE, Scicchitano D, Dolan ME
39. Comparison of repair of methylated pyrimidines in poly(dT) by extracts from rat liver and Escherichia coli.
    Biochem Biophys Res Commun (1984 Aug 30) PMID: 6383380
    Dolan ME, Scicchitano D, Singer B, Pegg AE
40. Kinetics of repair of O6-methylguanine in dna by O6-methylguanine-DNA methyltransferase in vitro and in vivo.
    Biochem Biophys Res Commun (1982 Dec 15) PMID: 7187611
    Scicchitano D, Pegg AE
41. Clinical experience in long-term anticoagulant therapy.
    Bull Geisinger (1962 Nov) PMID: 13992464
    SCICCHITANO DC