Skip to content
Articles by Adam Benjamin in JoVE
-
طريقة عملية ومبتكرة لاستخراج الحمض النووي الجينوم من الدم أطقم مجموعة لحفظ البلازما بروتين
Jon Waters1, Vishal Dhere1, Adam Benjamin1, Arvind Sekar1, Archana Kumar1, Sampath Prahalad2, David T. Okou1, Subra Kugathasan1
1Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta, 2Division of Rheumatology, Department of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta
نحن تصف طريقة جديدة لعزل الحمض النووي الجيني من الدم الكامل التي جمعت لبلازما / الأمصال. بعد جمع البلازما، ويتم عادة تجاهل الدم المضغوط. يمثل طريقة لدينا رواية تحسنا كبيرا خلال الأساليب القائمة ويجعل الحمض النووي والبلازما المتاحة من مجموعة واحدة، دون طلب دم إضافية.
Other articles by Adam Benjamin on PubMed
-
Fusion Tyrosine Kinase NPM-ALK Deregulates MSH2 and Suppresses DNA Mismatch Repair Function Novel Insights into a Potent Oncoprotein
The American Journal of Pathology.
Jul, 2011 |
Pubmed ID: 21703420 The fusion tyrosine kinase NPM-ALK is central to the pathogenesis of ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL). We recently identified that MSH2, a key DNA mismatch repair (MMR) protein integral to the suppression of tumorigenesis, is an NPM-ALK-interacting protein. In this study, we found in vitro evidence that enforced expression of NPM-ALK in HEK293 cells suppressed MMR function. Correlating with these findings, six of nine ALK(+)ALCL tumors displayed evidence of microsatellite instability, as opposed to none of the eight normal DNA control samples (P = 0.007, Student's t-test). Using co-immunoprecipitation, we found that increasing levels of NPM-ALK expression in HEK293 cells resulted in decreased levels of MSH6 bound to MSH2, whereas MSH2·NPM-ALK binding was increased. The NPM-ALK·MSH2 interaction was dependent on the activation/autophosphorylation of NPM-ALK, and the Y191 residue of NPM-ALK was a crucial site for this interaction and NPM-ALK-mediated MMR suppression. MSH2 was found to be tyrosine phosphorylated in the presence of NPM-ALK. Finally, NPM-ALK impeded the expected DNA damage-induced translocation of MSH2 out of the cytoplasm. To conclude, our data support a model in which the suppression of MMR by NPM-ALK is attributed to its ability to interfere with normal MSH2 biochemistry and function.
Get cutting-edge science videos from JoVE sent straight to your inbox every month.