Requirement for dicer in survival of proliferating thymocytes experiencing DNA double-strand breaks.
Requirement for dicer in survival of proliferating thymocytes experiencing DNA double-strand breaks.
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DOI：
10.4049/jimmunol.1200957
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发表时间：
2013-04-01
期刊：
影响因子：
--
通讯作者：
Bassing CH
中科院分区：
文献类型：
--
作者：
Brady BL;Rupp LJ;Bassing CH
The Dicer nuclease generates small RNAs that regulate diverse biological processes through post-transcriptional gene repression and epigenetic silencing of transcription and recombination. Dicer-deficient cells exhibit impaired differentiation, activity, proliferation, and survival. Dicer inactivation in developing mouse lymphocytes impairs their proliferation and survival and alters antigen receptor gene repertoires for largely undefined reasons. To elucidate functions of Dicer in lymphocyte development and antigen receptor locus transcription and recombination, we analyzed mice with conditional Dicer deletion in thymocytes containing un-rearranged or pre-rearranged TCRβ loci. Expression of either a pre-assembled functional TCRβ gene (Vβ1NT) or the pro-survival BCL2 protein inhibited death and partially rescued proliferative expansion of Dicer-deficient thymocytes. Notably, combined expression of Vβ1NT and BCL2 completely rescued proliferative expansion of Dicer-deficient thymocytes and revealed that Dicer promotes survival of cells attempting TCRβ recombination. Finally, inclusion of an endogenous pre-assembled DJβ complex that enhances Vβ recombination increased death and impaired proliferative expansion of Dicer-deficient thymocytes. These data demonstrate a critical role for Dicer in promoting survival of thymocytes experiencing DNA double strand breaks (DSBs) during TCRβ recombination. Since DSBs are common and ubiquitous in cells, our findings indicate that impaired cellular survival in response to DSBs should be considered when interpreting Dicer-deficient phenotypes.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
DOI：
10.1084/jem.20061692
发表时间：
2006-10-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cobb BS;Hertweck A;Smith J;O'Connor E;Graf D;Cook T;Smale ST;Sakaguchi S;Livesey FJ;Fisher AG;Merkenschlager M
通讯作者：
Merkenschlager M
DOI：
10.4049/jimmunol.1101079
发表时间：
2011-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brady BL;Bassing CH
通讯作者：
Bassing CH
影响因子：
64.5
作者：
Bassing, CH;Suh, H;Alt, FW
通讯作者：
Alt, FW
影响因子：
10.5
作者：
Chong, Mark M. W.;Zhang, Guoan;Littman, Dan R.
通讯作者：
Littman, Dan R.