Os cientistas descobriram que o complexo MCM desempenha um papel importante na restria§a£o da formaa§a£o de ala§as de DNA e, portanto, na estrutura tridimensional do genoma e na regulaa§a£o do gene.
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)
Para um empacotamento eficiente, o DNA écolocado em ala§as. O anel de coesina (rosa) forma a base para o laa§o. O complexo proteico MCM (amarelo) limita a formação da ala§a. Crédito: MPI de Bioquímica, Monika Krause
Todo o material gena´mico de uma canãlula deve ser empacotado em um minaºsculo núcleo celular de tal forma que, por um lado, possa ser armazenado de forma organizada e, por outro, possa ser transcrito, duplicado ou reparado como precisava. Diferentes proteanas são responsa¡veis ​​pelo empacotamento com economia de Espaço, que pode enrolar ou fazer um loop no DNA. Os cientistas Kikua« Tachibana e Karl Duderstadt do Instituto Max Planck de Bioquímica em Martinsried estãoinvestigando a tarefa e função exatas dessas ma¡quinas moleculares. Eles descobriram que o complexo MCM desempenha um papel importante na restrição da formação de ala§as de DNA e, portanto, na estrutura tridimensional do genoma e na regulação do gene.
Uma molanãcula de DNA tem cerca de dois metros de comprimento e ainda precisa ser empacotada em um minaºsculo núcleo de canãlula. Um núcleo de canãlula tem aproximadamente o tamanho de uma partacula de toner de uma impressora ou uma partacula de poeira fina. Como funciona? Como a informação genanãtica pode ser armazenada e empacotada por um lado, mas lida por outro? Como écolocado em loops? Empacotar e desembalar também são processos dina¢micos que devem ser executados de forma rápida e suave.
Agora Kikua« Tachibana, nova diretora do departamento "Totipotaªncia" do Instituto Max Planck de Bioquímica, e sua equipe descobriram que um complexo de proteanas conhecido por sua função na replicação do DNA tem um papel inesperado no dobramento do genoma. "Durante um simpa³sio em nosso instituto, surgiu que meu novo colega Karl Duderstadt e eu compartilhamos um interesse comum. Decidimos unir forças para usar abordagens complementares para investigar essas observações iniciais em umnívelmecanicista." Karl Duderstadt échefe do grupo de pesquisa "Estrutura e Dina¢mica de Ma¡quinas Moleculares".
Nova classe de barreiras
Neste estudo atual, eles já identificaram em conjunto o complexo de manutenção do minicromossomo (MCM) como uma nova classe de barreiras na formação de ala§as de DNA. No processo de formação da ala§a de DNA , também chamado de extrusão de ala§a, três proteanas ou complexos proteicos estãoenvolvidos principalmente: primeiro a coesina, segundo a proteana dedo de zinco CTCF e terceiro o complexo MCM. A coesina se liga ao DNA e inicia a formação de uma ala§a. A coesina enrola o DNA e isso resulta no crescimento progressivo de uma ala§a.
A extrusão de ala§a para quando a coesina encontra a proteana CTCF ligada ao DNA, que era a única barreira de extrusão de ala§a conhecida antes deste trabalho. "Embora os detalhes sejam diferentes, pode-se imaginar que éum pouco como colocar um anel em uma fita e passar a fita pelo anel, que permanece na base do laa§o", diz Matthias Scherr, co-autor do estudo. . Kikua« Tachibana explica: "Ao contra¡rio do CTCF, que éuma barreira especafica de vertebrados, os MCMs são conservados em eucariotos e archaea. Portanto, éfascinante considerar que isso pode ser uma barreira ancestral a extrusão de ala§as". O trabalho levanta a possibilidade de que os encontros de complexos de coesina de extrusão de ala§a com complexos de MCM sejam parte de um mecanismo fundamental que organiza o dobramento do genoma de uma ampla variedade de organismos.
Karl Duderstadt resume: "Nossa descoberta são foi possível atravanãs da formação de uma equipe internacional incravel com experiência em uma ampla gama de áreas. Este trabalho éuma prova do que épossível quando vocêconstra³i pontes entre os campos. Estou convencido de que muitas outras surpresas são reservado para nosa medida que exploramos mais profundamente a rede de interações que controlam a organização dos cromossomos."
O estudo foi publicado na Nature.