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Gil Chu Lab | Stanford Biochemistry | Copyright © 2013 | All Rights Reserved
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Our laboratory focuses on understanding how cells respond to DNA damage. To understand how DNA damaged by
ultraviolet radiation is targeted for repair, we identified UV-damaged DNA binding activity (UV-DDB). We showed:
that the DDB2 subunit of UV-DDB is mutated in xeroderma pigmentosum group E patients; that DNA damage induces
transcription of the DDB2 gene via a p53 response element; and that DDB2 enhances global genomic repair and
suppresses mutagenesis.

To understand how DNA double-strand breaks are repaired, we have characterized nonhomologous end-joining (NHEJ),
the pathway that repairs double-strand breaks produced by ionizing radiation and V(D)J recombination, the process
that generates immunological diversity. We showed: that Ku binds to DNA ends and recruits DNA-PKcs, which then
undergoes activation of its kinase domain; that cell extracts recapitulate in vivo NHEJ and require XRCC4/Ligase IV
to process the ends; and that Ku, XRCC4/Ligase IV and Cernunnos ligate mismatched non-cohesive ends.

\We invented methods for analyzing microarray data: Significance Analysis of Microarrays (SAM) identifies
genes with reproducible changes in expression and supplies a false detection rate from permutation of the data; and
Prediction Analysis of Microarrays (PAM) finds and cross-validates genes that classify a sample by proximity to the
nearest centroid for gene expression. We used these methods to find transcriptional responses to ionizing radiation
that predict toxicity from radiation therapy. These results provide hope that treatment toxicity can be predicted by a
clinical test.