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Bèl-2 inibit Nikleyè omolog rkonbinezon pa lokalizasyon BRCA1 Endomembranes yo

Source: http://cancerres.aacrjournals.org/content/71/10/3590.abstract

Author afilye

  1. Afilye Otè ': 1 CNRS, UMR217; 2 équipe labellisée «La championa 2008»; 3 plateforme de protéomique; 4 Institut de radyobyoloji seller et molekulèr, fontne aux roz; 5, URA2096 CNRS Laboratwa nan Trafik Manbràn, Saclay; 6 LRA17V, Université de 11 Pari-Sud, Orsay, Lafrans; ak 7 Max Planck Enstiti pou kou Biyoloji Pòtab Molecular ak Jenetik, Dresden, Almay
  1. Korespondan Author:
    Bernard S. Lopez, Institut de radyobyoloji seller et molekulèr, 18 wout du panorama, fontne aux roz F-92265, la Frans. Nimewo telefòn: 33-1-4654-8835; Faks: 33-1-4654-8955; E-mail: bernard.lopez @ cea.fr

Abstract

Estabilite jenetik mande pou kowòdinasyon pou yon rezo ki gen ladan repare wout ADN / rekonbinezon ak apoptozi. Anplis wòl kanonyal li yo anti-apoptotik, bèl-2 negatif enpak estabilite genomic. Nan etid sa a, nou idantifye tete timè kansè nan BRCA1 la antiparazit, ki jwe yon wòl enpòtan nan omolog rekonbinezon (HR), kòm yon objektif pou Bèl 2-nan represyon an HR. Vreman vre, yo yonizasyon radyasyon-pwovoke BRCA1 fwaye asanble te reprime lè Bèl-2 te eksprime ectopically, nan SV40 fibroblast imen, oswa natirèlman, nan lenfom selil T (14:18), ak nan HeLa ak liy H460 selil kansè. Anplis, nou te montre sa ki te transmanbranèr (TM) domèn lan nan Bèl 2-obligatwa pou tou de anpèchman nan BRCA1 fwaye asanble ak anpèchman nan HR pwovoke pa pran yon ti repo doub-Strand Theatre vize nan yon substra HR intrachromosomal pa meganuclease a I-SceI. Fluoresans mikwoskospi konfokal, épreuves litij distans, ak analyse mikwoskospi elèktron osi byen ke Western analiz efase non nan fraksyon subcellular te montre ke Bèl-2 ak BRCA1 colocalized reticulum mitokondri ak endoplasmic nan yon pwosesis ki mande domèn nan TM nan Bèl 2-. Vize BRCA1 endomembranes yo epwiz BRCA1 nan nwayo a ak, kidonk, kont pou anpèchman nan HR. Anplis de sa, konklizyon nou an sipò yon wòl apoptozi-stimulatory pou fòm nan cytosolic nan BRCA1, sijere ke yon nouvo timè fonksyon antiparazit nan BRCA1. Ansanm, rezilta nou yo revele yon mòd nouvo sou BRCA1 regilasyon ak pou Travay Resous Imèn nan antretyen an estabilite genomic. Res Kansè; 71 (10); 3590-602. © 2011 AACR.

Footnotes

Published (Last edited): 16-01-2012
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