کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1996971 1065529 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A Selective Requirement for 53BP1 in the Biological Response to Genomic Instability Induced by Brca1 Deficiency
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
A Selective Requirement for 53BP1 in the Biological Response to Genomic Instability Induced by Brca1 Deficiency
چکیده انگلیسی

SummaryThe molecular pathways leading from genomic instability to cellular senescence and/or cell death remain incompletely characterized. Using mouse embryonic fibroblasts with constitutively increased DNA damage due to the absence of the full-length form of the tumor suppressor Brca1 (Brca1Δ11/Δ11), we show that deletion of p53 binding protein 1 (53BP1) selectivity abrogates senescence and cell death stimulated by reduced Brca1 activity. Furthermore, the embryonic lethality induced by Brca1 mutation can be alleviated by 53BP1 deletion. Adult Brca1Δ11/Δ1153BP1−/− manifest constitutively high levels of genomic instability, yet age relatively normally, with a surprisingly low incidence of overall tumor formation. Together, these in vitro and in vivo data suggest that 53BP1 is specifically required for the development of premature senescence and apoptosis induced by Brca1 deficiency. These observations may have important implications for Brca1-mediated tumor formation as well as for the molecular pathway leading from genomic instability to organismal aging.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 35, Issue 4, 28 August 2009, Pages 534–541
نویسندگان
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