Home Faculty and Research Faculty by Name Stuart Linn

Stuart Linn

Professor of the Graduate School Division of Biochemistry and Molecular Biology*
*And Member, Graduate Groups in Biophysics and Comparative Biochemistry

Lab Homepage: http://mcb.berkeley.edu/labs/linn

Full Directory Information

Research Interests

Enzymes and DNA binding proteins involved in DNA damage responses, DNA repair and replication in mammalian cells. Mechanisms of DNA damage by reactive oxygen species. Iron-mediated free radical damages to DNA and the structure of iron: DNA complexes.

Current Projects

DNA damage and repair. We are interested in proteins from human cells that recognize DNA damage then directly or indirectly mediate the DNA damage response: DNA repair, transcription response, cell cycle arrest, or apoptosis. We are also studying carcinogenesis in mice lacking several of these proteins.

We are also interested in oxidative DNA damage caused by reactive oxygen species. These studies have led us to investigate how metal ions interact with DNA, in particular the sequence preferences for their binding.

DNA polymerases. We are interested in the properties of DNA polymerase of human cells, particularly changes which occur with these enzymes in various cell states and with various accessory factors. We are also interested in the roles of individual human DNA polymerases in  DNA replicative and repair synthesis.

Selected Publications

Itoh, T., Iwashita, S., Cohen, M.B., Meyerholz,  D. K., and Linn,  S.  (2007) DDB2 is a haplo-insufficient tumor suppressor and controls spontaneous germ cell apoptosis.  Human Molecular Genetics 16, 1578-1586.

Itoh, T. and Linn S.  (2007) The functions of mammalian DDB2 (XP-E) DNA Repair 6 (abstract).

 Itoh, T. and Linn, S. (2005).  The fate of p21CDKNIA in cells surviving UV-irradiation.  DNA Repair 4, 1457-1462.

Rai, P., Wemmer, D. E. and Linn, S. (2005) Preferential binding and structural distortion by Fe2+ at RGGG-containing DNA sequences correlates with enhanced oxidative cleavage at such sequences. Nuc. Acids Res. 33, 497-510.

Itoh, T., Cado, D., Kamide, R., and Linn, S. (2004) DDB2 gene disruption leads to skin tumors and resistance to apoptosis after exposure to ultraviolet light but not a chemical carcinogen. Proc. Nat'l. Acad. Sci. USA 101, 2052-2057.

Sancar, A., Lindsey-Boltz, L. A., Unsal-Kacmaz, K. and Linn, S. M. (2004). Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints. Ann. Rev. Bioch. 73, 39-85.

Asahara, H., Li, Y., Fuss, J., Hanes, D. S. Vlatkovic, N., Boyd, M. T., and Linn, S. (2003). Stimulation of Human DNA Polymerase e by MDM2. Nuc. Ac. Res. 31, 2451-2459.

Rai, P., Cole, T.D., Thompson, E., Millar, D., and Linn, S. (2003). Steady-state and time-resolved fluorescence studies indicate an unusual conformation of 2-aminopurine within ATAT and TATA duplex sequences. Nuc. Ac. Res. 31, 2323-2332.

Itoh, T., O'Shea, C. and Linn, S. (2003). Impaired Regulation of Tumor Suppressor p53 Caused by Mutations in the Xeroderma Pigmentosum DDB2 Gene: Mutual Regulatory Interactions between p48DDB2 and p53. Mol. Cell. Biol. 23, 7540-7553.

Brumaghim, J. L., Li, Y., Henle, E. and Linn, S. (2003). Effects of Hydrogen Peroxide upon Pyridine Nucleotide Metabolism in Escherichia coli: changes in Enzyme Levels and Pyridine Nucleotide Pools and Studies of the Oxidation of NAD(P)H by Fe(III). J. Biol. Chem. 278, 42495-42504.

Nichols, A. F., Itoh, T., Zolezzi, F., Hutsell, S., and Linn, S. (2003). Basal transcriptional activation of human damage-specific DNA binding genes DDB1 and DDB2 by sp1, E2F, N-MYC and NF1 elements. Nuc. Ac. Res. 31, 562-569.

Zolezzi, F., Fuss, J., Uzawa, S. and Linn, S. (2002). Characterization of a Schizosaccharomyces Pombe Strain Deleted for a Sequence Homologue of the Human Damaged DNA Binding 1 (DDB1) Gene. J. Biol. Chem. 277, 41183-41191.

Human DNA polymerase epsilon colocalizes with DNA replication late, but not early in S phase. [J. Fuss and S. Linn (2002) J. Biol. Chem. 277, 8658-8666]

Localization of Fe2+ at an RTGR Sequence within a DNA duplex explains preferential cleavage by Fe2+ and H202. [P. Rai, T. D. Cole, D. E. Wemmer and S. Linn (2001) J. Mol. Biol. 312, 1089-1101]

Abnormal Regulation of DDB2 Gene Expression in Xeroderma Pigmentosum Group E Strains. [T. Itoh, A. Nichols and S. Linn (2001) Oncogene 20, 7041-7050]

Proteolysis of the human DNA polymerase epsilon catalytic subunit by caspase-3 and calpain specifically during apoptosis. [W. Liu, and S. Linn (2000) Nuc. Ac. Res. 28, 4180-4188]

MDM2 interacts with the carboxy terminus of the catalytic subunit of DNA polymerase Epsilon. [N. Vlatkovic, S. Guerrera, Y. Li, S. Linn, D. S. Haines, and M. T. Boyd (2000) Nuc. Ac. Res.28, 3581-3586]

Identification and Cloning of Two Histone-fold Motif Containing Subunits of HeLa DNA Polymerase e. [Y. Li, Z. F. Pursell, and S. Linn (2000) J. Biol. Chem. 275, 23247-23252]

Nuclear Transport of Human DDB Protein Induced by Ultraviolet Light. [W. Liu, A. F. Nichols, J. A. Graham, R. Dualan, A. Abbas, and S. Linn (2000) J. Biol. Chem. 275, 21429-21434]

Human Damage-specific DNA Binding Protein p48: Characterization of XPE Mutations and Regulation Following UV-irradiation. [A. F. Nichols, T. Itoh, J. A. Graham, W. Liu, M. Yamaizumi, and S. Linn (2000) J. Biol. Chem. 275, 21422-21428]

Studies of the murine DDB1 and DDB2 genes. [F. Zolezzi and S. Linn (2000) Gene 245, 151-159]

The Naturally Occurring Mutants of DDB are Impaired in Stimulating Nuclear Import of the p125 Subunit and E2F1-Activated Transcription. [P. Shiyanov, S. A. Hayes, M. Donepudi, A. F. Nichols, S. Linn, B. L. Slagle, and P. Raychaudhuri (1999) Mol.Cell. Biol. 19, 4935-4943]

Sequence-specific DNA Cleavage by Fe2+-mediated Fenton Reactions has Possible Biological Implications. [E. S. Henle, Z. Han, N. Tang, P. Rai, Y. Luo, S. and Linn (1999) J. Biol. Chem. 274, 962-971]

Formation, Prevention and Repair of DNA Damage by Iron/Hydrogen Peroxide. [E. S. Henle and S. Linn (1997) J. Biol. Chem. 272, 19095-19098]

Purification, cDNA cloning and Gene Mapping of the Small Subunit of Human DNA Polymerase e. [Y. Li, H. Asahara, V. Patel, S. Zhou, and S. Linn (1997) J. Biol. Chem. 272, 32337-32344]

Mutations Accompanying the Xeroderma Pigmentosum Group E Ddb- Phenotype. [A. F. Nichols, P. Ong, and S. Linn (1996) J. Biol. Chem. 271, 24317-24320]

Fe2+, Fe3+ and Oxygen React with DNA-Derived Radicals Formed During Iron-Mediated Fenton Reactions. [E. S. Henle, Y. Luo, and S. Linn (1996) Biochemistry 35, 12212-12219]

Implication of Mammalian Ribosomal Protein S3 in the Processing of DNA Damage. [J. Kim, L. S. Chubatsu, A. Admon, J. Stahl, R. Fellous and S. Linn (1995) J. Biol. Chem. 270, 13620-13629]

Chromosomal Localization and cDNA Cloning of the Genes (DDB1 and DDB2) for the p127 and p48 Subunits of a Human Damage-Specific DNA Binding Protein. [R. Dualan, T. Brody, S. Keeney, A. F. Nichols, A. Admon and S. Linn (1995) Genomics 29, 62-69]

Purification of All Forms of HeLa Cell Mitochondrial DNA and Assessment of Damage to It Caused by Hydrogen Peroxide Treatment of Mitochondria or Cells. [Y. Higuchi and S. Linn (1995) J. Biol. Chem. 270, 7950-7956]

Last Updated 2007-07-31