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Woodgate Lab: Laboratory of Genomic Integrity

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Overview

Under optimal conditions, the fidelity of DNA replication is extremely high: it is estimated that, on average, only one error occurs in every 1010 bases replicated. However, as living organisms are continually subjected to a variety of endogenous and exogenous DNA-damaging agents, optimal conditions rarely occur in vivo. Even though all organisms have evolved elaborate repair pathways to deal with such damage, the pathways rarely operate with 100 percent efficiency.
As a consequence, cells have developed a mechanism for synthesizing past persisting DNA lesions, a process commonly referred to as translesion DNA synthesis (TLS) or translesion replication (TR). This process is thought to be facilitated by one or more of the “Y-family” of DNA polymerases that are phylogenetically conserved from bacteria to humans. The important role played by these polymerases in mutagenesis and carcinogenesis is typified by human pol eta, which can replicate past cis-syn thymine dimers very efficiently and relatively accurately. Humans with defects in pol eta are afflicted with the xeroderma pigmentosum variant phenotype and exhibit sensitivity to ultraviolet light and are prone to sunlight-induced skin cancers.

It is clear that many mutations are generated during the cell's attempts to facilitate replication past normally replication-blocking lesions. Our project aims to understand the molecular events that influence the fidelity of the genome, facilitating both evolution and species stability. We investigate the molecular mechanisms by which mutations are introduced into damaged DNA through TLS in all three kingdoms of life: bacteria, archaea, and eukaryotic cells. The dynamics of mutagenesis are also of interest, given the importance of mutations in genetic diseases, oncogenesis, and developmental abnormalities. Our studies involve a variety of molecular and biochemical techniques, including PCR, protein purification and characterization and yeast/bacterial molecular genetics.

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Last Updated Date: 11/30/2012
Last Reviewed Date: 11/30/2012

​Contact Information

Name: Dr Roger Woodgate
Senior Investigator
Section Laboratory of Genomic Integrity
Phone: 301-217-4040
Fax: 301-217-5815
E-mail: woodgate@mail.nih.gov

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