OBJECTIVES Nucleotide excision repair enzymes remove bulky damage caused by environmental agents, including carcinogenic polycyclic aromatic hydrocarbons found in cigarette smoke, a risk factor for colorectal adenoma. Among participants randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we studied the risk of advanced colorectal adenoma in rel...

Purpose: DNA repair capacity (DRC) is a determinant not only of cancer development but also of individual response to therapy. Previously, altered base and nucleotide excision repair (BER and NER) have been described in lymphocytes of patients with sporadic colorectal cancer. We, for the first time, evaluate both excision repair capacities in human colon biopsies to study their participation in...

Mammalian global genomic nucleotide excision repair requires lesion recognition by XPC, whose detailed binding mechanism remains to be elucidated. Here we have delineated the dynamic molecular pathway and energetics of lesion-specific and productive binding by the Rad4/yeast XPC lesion recognition factor, as it forms the open complex [Min, J. H., and Pavletich, N. P. (2007) Nature 449, 570-575;...

The entire process of nucleotide excision repair (NER) in Escherichia coli has been reconstituted in vitro from purified proteins and defined DNA substrates. However, how this system is organized in vivo in unclear. We report here the isolation and characterization of macromolecular assemblies containing NER and transcription proteins from E. coli. This ensemble consists of at least 17 proteins...

The physicochemical constitution of DNA cannot warrant lifelong stability. Yet, unlike all other macromolecules, nuclear DNA must last the lifetime of a cell ensuring that its vital genetic information is preserved and faithfully transmitted to progeny. An increasing body of evidence suggests that progressive genome instability likely contributes to aging and shortens lifespan. In support, defe...

Schizosaccharomyces pombe cells deficient in nucleotide excision repair (NER) are still able to remove photoproducts from cellular DNA, showing that there is a second pathway for repair of UV damage in this organism. We have characterized this repair pathway by cloning and disruption of the genomic gene encoding UV damage endonuclease (UVDE). Although uvde gene disruptant cells are only mildly ...

Rad4p is a DNA damage recognition protein essential for global genomic nucleotide excision repair in Saccharomyces cerevisiae. Here, we show that Rad4p binds to the heterochromatic HML locus. In a yeast mutant lacking Rad4p, an increased level of SIR complex binding at the HML locus is accompanied by an altered, more compact heterochromatin structure, as revealed by a topological analysis of ch...

We propose a nonlinear model derived from first principles, to describe bubble dynamics of DNA. Our model equations include a term derived from the dissipative effect of intermolecular vibrational modes. Such modes are excited by the propagating bubble, and we term this 'curvature dissipation'. The equations that we derive allow for stable pinned localized kinks which form the bubble. We perfor...

INTRODUCTION Can a single polymorphic site help tailor a cancer patient’s chemotherapy regimen? The study by Zhao et al. (1) presented in this issue of Clinical Cancer Research suggests that in fact polymorphic sites in noncoding gene regions may determine how a patient will react to a given chemotherapy and the likelihood of cancer recurrence after treatment. The group focused their investigat...