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In Silico Construction of a Protein Interaction Landscape for Nucleotide Excision Repair

Cell Biochemistry and Biophysics volume 53, pages 101–114 (2009)Cite this article

Abstract

To obtain a systems-level perspective on the topological and functional relationships among proteins contributing to nucleotide excision repair (NER) in Saccharomyces cerevisiae, we built two models to analyze protein–protein physical interactions. A recursive computational model based on set theory systematically computed overlaps among protein interaction neighborhoods. A statistical model scored computation results to detect significant overlaps which exposed protein modules and hubs concurrently. We used these protein entities to guide the construction of a multi-resolution landscape which showed relationships among NER, transcription, DNA replication, chromatin remodeling, and cell cycle regulation. Literature curation was used to support the biological significance of identified modules and hubs. The NER landscape revealed a hierarchical topology and a recurrent pattern of kernel modules coupling a variety of proteins in structures that provide diverse functions. Our analysis offers a computational framework that can be applied to construct landscapes for other biological processes.

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Acknowledgments

We thank Keziban Űnsal-Kaçmaz and Marila Cordeiro-Stone for helpful discussions and ideas and Dan Reed for initial support of this work. Nancy Tran was supported by the Leon and Bertha Goldberg Fellowship. Funding was also provided by PHS grants (ES014635, ES011391, ES010126, CA081343, GM070335, CA074015) and NSF grants to the National Center for Supercomputing Applications (CA SCI-0525308 and CSA SCI-0438712).

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Affiliations

  1. Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Nancy Tran, Dennis A. Simpson & William K. Kaufmann

  2. Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Ping-Ping Qu & Joseph G. Ibrahim

  3. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Laura Lindsey-Boltz

  4. Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Xiaojun Guan & Charles P. Schmitt

  5. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Joseph G. Ibrahim & William K. Kaufmann

  6. Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Joseph G. Ibrahim & William K. Kaufmann

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  1. Nancy Tran
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  2. Ping-Ping Qu
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  3. Dennis A. Simpson
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Correspondence to William K. Kaufmann.

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Tran, N., Qu, PP., Simpson, D.A. et al. In Silico Construction of a Protein Interaction Landscape for Nucleotide Excision Repair. Cell Biochem Biophys 53, 101–114 (2009). https://doi.org/10.1007/s12013-009-9042-y

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  • DOI: https://doi.org/10.1007/s12013-009-9042-y

Keywords

  • DNA repair
  • Excision
  • Network
  • Computation