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I am a Senior Research Scientist in the laboratory of Phil Hanawalt
, Biological Sciences Department, Stanford University. I have been studying the mechanisms of DNA repair in human cells for many years; my most current efforts have been concentrated on the elucidation of the biochemical basis for the human hereditary diseases, UV-sensitive syndrome (UVS
S) and Cockayne syndrome (CS). Individuals with these syndromes carry mutations in the CSA
genes, or in a third gene in some UVS
S cases, UVSSA
; they are extremely sun-sensitive, but they are not abnormally prone to cancer. Cells from UVS
S and CS individuals are deficient in transcription-coupled repair (TCR) of "bulky" DNA adducts. The clinical hallmarks of CS include neurological/developmental abnormalities and premature aging. UVS
S cells are not sensitive to inducers of oxidative damage that are notably cytotoxic in cells from CS patients. Our findings imply that some mutations in the CSA
genes may interfere with the TCR-dependent removal of UV-induced damage, without affecting their role in the oxidative stress response. The differential sensitivity toward oxidative stress might explain the difference between the range and severity of symptoms in CS and the mild manifestations in UVS
S patients that are limited to skin photosensitivity without precocious aging or neurodegeneration. However, we have recently shown that both CS and UVS
S cells are defective in TCR of the oxidized lesion 8-oxoGuanine. hOGG1 and XPA are also required for TCR of these lesions; I am currently investigating which other factors are involved in what appears to be a case of crosstalk between the base excision and nucleotide excision repair pathways.
The Hanawalt Lab Group
The photo was taken near Herrin Labs, Stanford University, in the summer of 2011. From left to right, top row: Gisela Poletta, visiting scholar from Argentina; Allen Smith, emeritus Senior Scientist; Ann Pipathsouk, undergrad; Silvan Göldi, visiting student from Switzerland; Jia Guo, senior postdoc; Yolanda Madrid, admin; Alex Neil, undergrad; Jane Shin, undergrad; Boris Belotserkovskii, research associate; Shristi Pandey, undergrad; bottom row: Graciela Spivak, senior research scientist; Phil Hanawalt, professor; Ann Ganesan, emerita senior research scientist. Marcela Gona, technician: not shown.
- Ganesan A.K., Spivak G. and Hanawalt P.C. (1983) "Expression of DNA repair genes in mammalian cells" in Manipulation and Expression of Genes in Eukaryotes, P. Nagley, A.W. Linnane, W.J. Peacock, J.A. Pateman (eds.) pp. 45-54, Academic Press, Australia.
- Spivak G. Ganesan A.K. and Hanawalt P.C. (1984) Enhanced transformation of human cells by UV irradiated pSV2 plasmids, Mol. Cell. Biol. 4:1169-1171.
- Mellon I., Spivak G. and Hanawalt P.C. (1987) Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian genome, Cell 51:241-249.
- Spivak G., Leadon S.A., Vos J-M, Ganesan A.K. and Hanawalt P.C. (1987) "Transformation of human cells with damaged plasmids", in Proceedings of the 14th. International Cancer Congress, pp. 107-117, Budapest, Hungary.
- Mellon I., Spivak G. and Hanawalt P.C. (1988) "Selective strand repair in CHO cells containing heterologous repair genes", in Mechanisms and Consequences of DNA Damage Processing, UCLA Symposia on Molecular and Cell biology, E.C. Friedberg and P.C. Hanawalt (eds.) 83:263-266.
- Spivak G., Leadon S.A., Vos J-M, Meade S., Hanawalt P.C. and Ganesan A.K. (1988) Enhanced transforming activity of pSV2 plasmids in human cells depends upon the type of damage introduced into the plasmid, Mutat. Res. 193:97-108.
- Ganesan A.K. and Spivak G. (1988) "Use of shuttle vectors for analysis of DNA damage processing" in DNA Repair: A Laboratory Manual Of Research Procedures, vol. 3, E.C. Friedberg and P.C. Hanawalt (eds.) pp. 295-308, Marcel Dekker, New York.
- Mellon I., Spivak G. and Hanawalt P.C. (1989) "Selective DNA repair in the transcribed strands of active genes in mammalian cells", in Proceedings of the International Congress on DNA Damage and Repair, Castellani A. (ed.) pp. 37-42, Plenum Press, New York.
- Hanawalt P.C., Mellon I., Scicchitano D.A. and Spivak G. (1989) "Relationships between repair and transcription in defined DNA sequences in mammalian cells", In DNA Repair Mechanisms And Their Biological Implications In Mammalian Cells, Lambert M.W. and Laval J. (eds.) pp. 325-337, Plenum Publishing Corp., New York.
- Spivak G. and Hanawalt P.C. (1992) Translesion DNA synthesis in the dihydrofolate reductase domain of UV-irradiated CHO cells, Biochemistry 31:6794-6800.
- Baird W.M., Smith C.A., Spivak G., Mauthe R.J. and Hanawalt P.C.(1994) Analysis of the fine structure of the repair of anti-benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts in mammalian cells by laser-induced strand cleavage, Polycyclic Aromatic Compounds 6: 169-176.
- Spivak G. and Hanawalt P.C. (1995) Determination of damage and repair in specific DNA sequences, in Methods: A Companion to Methods in Enzymology 7:147-161.
- Spivak G. and Hanawalt P.C. (1996) Fine structure mapping of DNA repair within a 100 kb genomic region in Chinese hamster ovary cells, Mutat. Res. 350:207-216.
- Hanawalt P.C. and Spivak G. (1999) "Transcription-coupled repair: Which lesions? Which diseases?", in Advances in DNA damage and repair, Dizdaroglu and Karakaya (eds.), Plenum Press, New York, pp. 169-179.
- Hanawalt P.C., Crowley D.J., Ford J.M., Ganesan A.K., Lloyd D.R., Nouspikel T., Smith C.A., Spivak G., Tornaletti S. (2001) "Regulation of nucleotide excision repair in bacteria and mammalian cells", in Cold Spring Harbor Symposia on Quantitative Biology, vol 65, pp. 183-191, Cold Spring Harbor Laboratory Press.
- Spivak G., Itoh T., Matsunaga T., Nikaido O., Hanawalt P.C. and Yamaizumi M. (2002) UV-sensitive syndrome cells are defective in transcription-coupled repair of cyclobutane pyrimidine dimers, DNA Repair 1:629-643.
- Spivak G., Lloyd R.S. and Sweder K.S. (2003) Workshop on DNA Repair and Related DNA Transactions, a Conference Report, DNA Repair 2:235-242.
- Spivak G. (2004) The many faces of Cockayne syndrome, Proc. Natl. Acad. Sci. USA 101:15273-15274.
- Xu G., Spivak G., Mitchell D.L., Mori T., McCarrey J.R., McMahan C.A., Walter R.B., Hanawalt P.C. and Walter C.A. (2005) Nucleotide excision repair in mice declines during spermatogenesis and is modulated by age, Biol. of Reprod., 73:123-130.
- Spivak G. (2005) UV-sensitive syndrome, Mutat. Res. 577:162-169.
- Spivak G. and Hanawalt P.C. (2006) Host cell reactivation of plasmids containing oxidative DNA lesions is defective in Cockayne syndrome but normal in UV-sensitive syndrome, DNA Repair, 5:13-22.
- Spivak G., Pfeifer G. and Hanawalt P.C. (2006) In vivo assays for transcription-coupled repair, in "DNA Repair, Methods in Enzymology", Modrich P. and Campbell J. (eds.), vol 408, pp. 223-246, Elsevier.
- Spivak G., Cox R.A. and Hanawalt P.C. (2008) New Applications of the Comet Assay: Comet-FISH and Transcription-Coupled DNA Repair, Mutat Res. 681:44-50.
- Hanawalt P. C. and Spivak G. (2008) Transcription-coupled DNA repair: two decades of progress and surprises. Nat. Rev. Mol. Cell Biol. 9(12):958-970.
- Nardo T., Oneda R., Spivak G., Vaz B., Mortier L., Thomas P., Orioli D., Laugel V., Stary A., Hanawalt P.C., Sarasin A. and Stefanini M. (2009) Identification of a UV-sensitive syndrome patient mutated in the CSA gene: a third complementation group. Proc. Natl. Acad. Sci. USA 106(15):6209-6214.
- Hanawalt P. C. and Spivak G. (2009) Preface for the volume “Molecular Mechanisms
of Cockayne Syndrome”, Ahmad S. I. (ed.), Landes Biosciences.
- Spivak G. and Oh D. (2009) Hereditary Photodermatoses, in “Diseases of DNA Repair”, Ahmad S. I. (ed.), Landes Biosciences, www.landesbioscience.com/curiechapter/4419/.
- Olivero O., Larramendy M., Soloneski S., Menck C. F. M., Matta J., Folle G. A., Zamorano-Ponce E. and Spivak G. (2010) Impact of EMS Outreach: Successful Developments in Latin America, Env. Molec. Mutagen., epub ahead of print PMID: 20213840.
- Spivak, G (2010) The Comet-FISH Assay for Analysis of DNA Damage and Repair, Methods in Molecular Biology 659:129-145.
- Falik-Zaccai, T. C., Erel-Segal R., Horev L., Bitterman-Deutsch O., Koka S., Chaim S., Zohar K., Limor K., Gross B., Segal Z., Orgal S., Shoval Y., Slor H., Spivak G. and Hanawalt P. C. (2012) A novel XPD mutation in a compound heterozygote; the mutation in the second allele is present in three homozygous patients with mild sun sensitivity. Env. Molec. Mutagen., in press.
- Hanawalt, P. C., Spivak G., Ganesan, A. K. (2012) “Transcription-coupled DNA repair in prokaryotes”, in Mechanisms of DNA Repair, Vol. 110, Doetsch P. ed., Academic Press, pp. 25-40.
- Guo J, Hanawalt PC, Spivak G. (2013) Comet-FISH with strand-specific probes reveals transcription-coupled repair of 8-oxoGuanine in human cells, Nucleic Acids Res. 41(6):7700-7712.
- Spivak G., Ganesan A. K. (2014) The complex choreography of transcription-coupled repair, DNA Repair 19:64-70.
- Spivak G., Hanawalt P. C. (2014) Photosensitive human syndromes, Mutation Research 10.1016/j.mrfmmm.2014.11.003.
- Spivak G. (2014) New developments in Comet-FISH, Mutagenesis, in press.
Last Updated: December 1, 2014
Stanford CA 94305-5020