Stéphane Vispé

Bio: Stéphane Vispé is an academic researcher from Laval University. The author has contributed to research in topics: DNA clamp & DNA polymerase II. The author has an hindex of 4, co-authored 4 publications receiving 157 citations.

A cellular defense pathway regulating transcription through poly(ADP-ribosyl)ation in response to DNA damage

Abstract: DNA damage is known to trigger key cellular defense pathways such as those involved in DNA repair. Here we provide evidence for a previously unrecognized pathway regulating transcription in response to DNA damage and show that this regulation is mediated by the abundant nuclear enzyme poly(ADP-ribose) polymerase. We found that poly(ADP-ribose) polymerase reduced the rate of transcription elongation by RNA polymerase II, suggesting that poly(ADP-ribose) polymerase negatively regulates transcription, possibly through the formation of poly(ADP-ribose) polymerase–RNA complexes. In damaged cells, poly(ADP-ribose) polymerase binds to DNA breaks and automodifies itself in the presence of NAD+, resulting in poly(ADP-ribose) polymerase inactivation. We found that automodification of poly(ADP-ribose) polymerase in response to DNA damage resulted in the up-regulation of transcription, presumably because automodified poly(ADP-ribose) polymerase molecules were released from transcripts, thereby relieving the block on transcription. Because agents that damage DNA damage RNA as well, up-regulation of RNA synthesis in response to DNA damage may provide cells with a mechanism to compensate for the loss of damaged transcripts and may be critical for cell survival after exposure to DNA-damaging agents.

Polymorphisms in DNA repair genes and associations with cancer risk.

Abstract: Common polymorphisms in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. To establish our overall understanding of possible in vivo relationships between DNA repair polymorphisms and the development of cancer, we performed a literature review of epidemiological studies that assessed associations between such polymorphisms and risk of cancer. Thirty studies of polymorphisms in OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and XRCC3 were identified in the April 30, 2002 MEDLINE database (National Center for Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez). These studies focused on adult glioma, bladder cancer, breast cancer, esophageal cancer, lung cancer, prostate cancer, skin cancer (melanoma and nonmelanoma), squamous cell carcinoma of the head and neck, and stomach cancer. We found that a small proportion of the published studies were large and population-based. Nonetheless, published data were consistent with associations between: (a) the OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer. Suggestive results were seen for polymorphisms in other genes; however, small sample sizes may have contributed to false-positive or false-negative findings. We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of cancer in the presence of reduced DNA repair capacity.

Survey of the year 2003 commercial optical biosensor literature

Abstract: In the year 2003 there was a 17% increase in the number of publications citing work performed using optical biosensor technology compared with the previous year. We collated the 962 total papers for 2003, identified the geographical regions where the work was performed, highlighted the instrument types on which it was carried out, and segregated the papers by biological system. In this overview, we spotlight 13 papers that should be on everyone's 'must read' list for 2003 and provide examples of how to identify and interpret high-quality biosensor data. Although we still find that the literature is replete with poorly performed experiments, over-interpreted results and a general lack of understanding of data analysis, we are optimistic that these shortcomings will be addressed as biosensor technology continues to mature.

Flap Endonuclease 1: A Central Component of DNA Metabolism

Abstract: ▪ Abstract One strand of cellular DNA is generated as RNA-initiated discontinuous segments called Okazaki fragments that later are joined. The RNA terminated region is displaced into a 5′ single-stranded flap, which is removed by the structure-specific flap endonuclease 1 (FEN1), leaving a nick for ligation. Similarly, in long-patch base excision repair, a damaged nucleotide is displaced into a flap and removed by FEN1. FEN1 is a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. As an endonuclease, FEN1 enters the flap from the 5′ end and then tracks to cleave the flap base. Cleavage is oriented by the formation of a double flap. Analyses of FEN1 crystal structures suggest mechanisms for tracking and cleavage. Some flaps can form self-annealed and template bubble structures that interfere with FEN1. FEN1 interacts with other nucleases and helicases that allow it to act efficiently on structured flaps. Genetic and biochemical analyse...