title: In silico construction of a protein interaction landscape for nucleotide excision repair.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Tran
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Qu
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Simpson
authors.forename: Laura
authors.initials: L
authors.lastname: Lindsey-Boltz
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Guan
authors.forename: Charles P
authors.initials: CP
authors.lastname: Schmitt
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Ibrahim
authors.forename: William K
authors.initials: WK
authors.lastname: Kaufmann
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002453:Cell Cycle; D042002:Chromatin Assembly and Disassembly; D019295:Computational Biology; D003198:Computer Simulation; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004261:DNA Replication; D030541:Databases, Genetic; D003851:Deoxyribonucleases / Q000378:metabolism; D016681:Genome, Fungal; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D051758:Transcription Factor TFIIH / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C072975:RAD14 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C517874:Tfb5 protein, S cerevisiae; D051758:Transcription Factor TFIIH; D003851:Deoxyribonucleases; D000251:Adenosine Triphosphatases; C061897:Rad3 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes