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dc.contributor.authorCastro, Mauro Antônio Alvespt_BR
dc.contributor.authorDalmolin, Rodrigo Juliani Siqueirapt_BR
dc.contributor.authorMoreira, Jose Claudio Fonsecapt_BR
dc.contributor.authorMombach, Jose Carlos Merinopt_BR
dc.contributor.authorAlmeida, Rita Maria Cunha dept_BR
dc.date.accessioned2010-05-05T04:15:51Zpt_BR
dc.date.issued2008pt_BR
dc.identifier.issn0305-1048pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/21551pt_BR
dc.description.abstractApoptosis is essential for complex multicellular organisms and its failure is associated with genome instability and cancer. Interactions between apoptosis and genome-maintenance mechanisms have been extensively documented and include transactivation-independent and -dependent functions, in which the tumor-suppressor protein p53 works as a ‘molecular node’ in the DNA-damage response. Although apoptosis and genome stability have been identified as ancient pathways in eukaryote phylogeny, the biological evolution underlying the emergence of an integrated system remains largely unknown. Here, using computational methods, we reconstruct the evolutionary scenario that linked apoptosis with genome stability pathways in a functional human gene/protein association network. We found that the entanglement of DNA repair, chromosome stability and apoptosis gene networks appears with the caspase gene family and the antiapoptotic gene BCL2. Also, several critical nodes that entangle apoptosis and genome stability are cancer genes (e.g. ATM, BRCA1, BRCA2, MLH1, MSH2, MSH6 and TP53), although their orthologs have arisen in different points of evolution. Our results demonstrate how genome stability and apoptosis were co-opted during evolution recruiting genes that merge both systems. We also provide several examples to exploit this evolutionary platform, where we have judiciously extended information on gene essentiality inferred from model organisms to human.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.relation.ispartofNucleic acids research. Oxford. Vol. 36, no. 19 (Nov. 2008), p. 6269-6283pt_BR
dc.rightsOpen Accessen
dc.subjectGenéticapt_BR
dc.subjectReparação do DNApt_BR
dc.subjectRedes reguladoras de genespt_BR
dc.subjectNeoplasiaspt_BR
dc.subjectGenes p53pt_BR
dc.subjectEscherichia colipt_BR
dc.titleEvolutionary origins of human apoptosis and genome-stability gene networkspt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb000684184pt_BR
dc.type.originEstrangeiropt_BR


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