Evolutionary origins of human apoptosis and genome-stability gene networks
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/21551 |
Resumo: | Apoptosis 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. |
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Castro, Mauro Antônio AlvesDalmolin, Rodrigo Juliani SiqueiraMoreira, Jose Claudio FonsecaMombach, Jose Carlos MerinoAlmeida, Rita Maria Cunha de2010-05-05T04:15:51Z20080305-1048http://hdl.handle.net/10183/21551000684184Apoptosis 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.application/pdfengNucleic acids research. Oxford. Vol. 36, no. 19 (Nov. 2008), p. 6269-6283GenéticaReparação do DNARedes reguladoras de genesNeoplasiasGenes p53Escherichia coliEvolutionary origins of human apoptosis and genome-stability gene networksEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL000684184.pdf000684184.pdfTexto completo (inglês)application/pdf1132396http://www.lume.ufrgs.br/bitstream/10183/21551/1/000684184.pdffd12ede0cbef57f345b7b8f4bc3e16b0MD51TEXT000684184.pdf.txt000684184.pdf.txtExtracted Texttext/plain77078http://www.lume.ufrgs.br/bitstream/10183/21551/2/000684184.pdf.txt973b2e6368e0e1407f4c80da05faedc1MD52THUMBNAIL000684184.pdf.jpg000684184.pdf.jpgGenerated Thumbnailimage/jpeg2221http://www.lume.ufrgs.br/bitstream/10183/21551/3/000684184.pdf.jpg6a57839b0f86bedadda44190589b1f1dMD5310183/215512024-03-29 06:19:48.495117oai:www.lume.ufrgs.br:10183/21551Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2024-03-29T09:19:48Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Evolutionary origins of human apoptosis and genome-stability gene networks |
title |
Evolutionary origins of human apoptosis and genome-stability gene networks |
spellingShingle |
Evolutionary origins of human apoptosis and genome-stability gene networks Castro, Mauro Antônio Alves Genética Reparação do DNA Redes reguladoras de genes Neoplasias Genes p53 Escherichia coli |
title_short |
Evolutionary origins of human apoptosis and genome-stability gene networks |
title_full |
Evolutionary origins of human apoptosis and genome-stability gene networks |
title_fullStr |
Evolutionary origins of human apoptosis and genome-stability gene networks |
title_full_unstemmed |
Evolutionary origins of human apoptosis and genome-stability gene networks |
title_sort |
Evolutionary origins of human apoptosis and genome-stability gene networks |
author |
Castro, Mauro Antônio Alves |
author_facet |
Castro, Mauro Antônio Alves Dalmolin, Rodrigo Juliani Siqueira Moreira, Jose Claudio Fonseca Mombach, Jose Carlos Merino Almeida, Rita Maria Cunha de |
author_role |
author |
author2 |
Dalmolin, Rodrigo Juliani Siqueira Moreira, Jose Claudio Fonseca Mombach, Jose Carlos Merino Almeida, Rita Maria Cunha de |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Castro, Mauro Antônio Alves Dalmolin, Rodrigo Juliani Siqueira Moreira, Jose Claudio Fonseca Mombach, Jose Carlos Merino Almeida, Rita Maria Cunha de |
dc.subject.por.fl_str_mv |
Genética Reparação do DNA Redes reguladoras de genes Neoplasias Genes p53 Escherichia coli |
topic |
Genética Reparação do DNA Redes reguladoras de genes Neoplasias Genes p53 Escherichia coli |
description |
Apoptosis 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. |
publishDate |
2008 |
dc.date.issued.fl_str_mv |
2008 |
dc.date.accessioned.fl_str_mv |
2010-05-05T04:15:51Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
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article |
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http://hdl.handle.net/10183/21551 |
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0305-1048 |
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000684184 |
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0305-1048 000684184 |
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http://hdl.handle.net/10183/21551 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Nucleic acids research. Oxford. Vol. 36, no. 19 (Nov. 2008), p. 6269-6283 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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