Cell Biochemistry and Biophysics

, Volume 53, Issue 2, pp 101–114 | Cite as

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

  • Nancy Tran
  • Ping-Ping Qu
  • Dennis A. Simpson
  • Laura Lindsey-Boltz
  • Xiaojun Guan
  • Charles P. Schmitt
  • Joseph G. Ibrahim
  • William K. Kaufmann
Original Paper


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.


DNA repair Excision Network Computation 



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).

Supplementary material

12013_2009_9042_MOESM1_ESM.pdf (127 kb)
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12013_2009_9042_MOESM2_ESM.pdf (104 kb)
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12013_2009_9042_MOESM3_ESM.pdf (91 kb)
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Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Nancy Tran
    • 1
  • Ping-Ping Qu
    • 2
  • Dennis A. Simpson
    • 1
  • Laura Lindsey-Boltz
    • 3
  • Xiaojun Guan
    • 4
  • Charles P. Schmitt
    • 4
  • Joseph G. Ibrahim
    • 2
    • 5
    • 6
  • William K. Kaufmann
    • 1
    • 5
    • 6
  1. 1.Department of Pathology and Laboratory MedicineUniversity of North Carolina at Chapel HillChapel HillUSA
  2. 2.Department of BiostatisticsUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.Department of Biochemistry and BiophysicsUniversity of North Carolina at Chapel HillChapel HillUSA
  4. 4.Renaissance Computing InstituteUniversity of North Carolina at Chapel HillChapel HillUSA
  5. 5.Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillChapel HillUSA
  6. 6.Center for Environmental Health and SusceptibilityUniversity of North Carolina at Chapel HillChapel HillUSA

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