Philip C. Hanawalt, Stanford University
Professor
Stanford, California
hanawalt@stanford.edu
Office:
(650) 723-2424
Expert In
Bio/Research
Transcription effects on genomic instability with non-canonical DNA structures
Hanawalt has been a productive researcher in the field of DNA repair since his pioneering discovery of repair replication in E. coli in 1963. In 1982 Hanawalt and his colleagues reported the first ex...
Click to Expand >>
Hanawalt has been a productive researcher in the field of DNA repair since his pioneering discovery of repair replication in E. coli in 1963. In 1982 Hanawalt and his colleagues reported the first ex...
Click to Expand >>
Bio/Research
Transcription effects on genomic instability with non-canonical DNA structures
Hanawalt has been a productive researcher in the field of DNA repair since his pioneering discovery of repair replication in E. coli in 1963. In 1982 Hanawalt and his colleagues reported the first example of intragenomic DNA repair heterogeneity: chemical adducts in alpha DNA in African green monkey kidney cells were not as efficiently repaired as in the genome overall. Hanawalt and his colleagues then discovered that repair of some types of damage is selective; active genes are preferentially repaired, and in fact a special repair pathway, termed transcription-coupled repair (TCR), operates on the transcribed strands of expressed genes. TCR was documented in mammalian cells, in E. coli, and in yeast chromosomal and plasmid borne genes. The discovery of TCR in Hanawalts laboratory has had profound implications for the fields of mutagenesis, environmental carcinogenesis, aging, and risk assessment.
The prototype recQ gene was discovered in E. coli in Hanawalts laboratory, and we now know of five homologues in humans including the genes mutated in the cancer prone hereditary diseases: Blooms syndrome, Werners syndrome, and Rothman Thompson syndrome.
More recent studies have focused upon the regulation of TCR and the global genomic nucleotide excision repair (GGR) pathway. Features of the TCR pathway (defective in Cockayne syndrome) include the possibility of "gratuitous TCR" at transcription pause sites in undamaged DNA. The GGR pathway was shown to be controlled through the SOS stress response in E. coli and through the activated product of the p53 tumor suppressor gene in human cells. These regulatory systems particularly affect the efficiency of repair of the predominant UV-induced photoproduct, the cyclobutane pyrimidine dimer, as well as that of chemical carcinogen DNA adducts, such as benzo(a)pyrene diol-epoxide and benzo(g)chrysene. Rodent cells (typically lacking the p53-controlled GGR pathway) are unable to carry out efficient GGR of some lesions. Therefore, caution should be exercised in the interpretation of results from such systems for risk assessment in genetic toxicology.
Click to Shrink <<
Hanawalt has been a productive researcher in the field of DNA repair since his pioneering discovery of repair replication in E. coli in 1963. In 1982 Hanawalt and his colleagues reported the first example of intragenomic DNA repair heterogeneity: chemical adducts in alpha DNA in African green monkey kidney cells were not as efficiently repaired as in the genome overall. Hanawalt and his colleagues then discovered that repair of some types of damage is selective; active genes are preferentially repaired, and in fact a special repair pathway, termed transcription-coupled repair (TCR), operates on the transcribed strands of expressed genes. TCR was documented in mammalian cells, in E. coli, and in yeast chromosomal and plasmid borne genes. The discovery of TCR in Hanawalts laboratory has had profound implications for the fields of mutagenesis, environmental carcinogenesis, aging, and risk assessment.
The prototype recQ gene was discovered in E. coli in Hanawalts laboratory, and we now know of five homologues in humans including the genes mutated in the cancer prone hereditary diseases: Blooms syndrome, Werners syndrome, and Rothman Thompson syndrome.
More recent studies have focused upon the regulation of TCR and the global genomic nucleotide excision repair (GGR) pathway. Features of the TCR pathway (defective in Cockayne syndrome) include the possibility of "gratuitous TCR" at transcription pause sites in undamaged DNA. The GGR pathway was shown to be controlled through the SOS stress response in E. coli and through the activated product of the p53 tumor suppressor gene in human cells. These regulatory systems particularly affect the efficiency of repair of the predominant UV-induced photoproduct, the cyclobutane pyrimidine dimer, as well as that of chemical carcinogen DNA adducts, such as benzo(a)pyrene diol-epoxide and benzo(g)chrysene. Rodent cells (typically lacking the p53-controlled GGR pathway) are unable to carry out efficient GGR of some lesions. Therefore, caution should be exercised in the interpretation of results from such systems for risk assessment in genetic toxicology.
Click to Shrink <<