The ataxia telangiectasia mutated and cyclin D3 proteins cooperate to help enforce TCRβ and IgH allelic exclusion.
The ataxia telangiectasia mutated and cyclin D3 proteins cooperate to help enforce TCRβ and IgH allelic exclusion.
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DOI：
10.4049/jimmunol.1302201
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发表时间：
2014-09-15
期刊：
影响因子：
--
通讯作者：
Bassing CH
中科院分区：
文献类型：
--
作者：
Steinel NC;Fisher MR;Yang-Iott KS;Bassing CH
Coordination of V rearrangements between loci on homologous chromosomes is critical for Ig and TCR allelic exclusion. The Ataxia Telangietasia mutated (ATM) protein kinase promotes DNA repair and activates checkpoints to suppress aberrant Ig and TCR rearrangements. In response to RAG cleavage of Igκ loci, ATM inhibits RAG expression and suppresses further Vκ-to-Jκ rearrangements to enforce Igκ allelic exclusion. Since V recombination between alleles is more strictly regulated for TCRβ and IgH loci, we evaluated the ability of ATM to restrict bi-allelic expression and V-to-DJ recombination of TCRβ and IgH genes. We detected greater frequencies of lymphocytes with bi-allelic expression or aberrant V-to-DJ rearrangement of TCRβ or IgH loci in mice lacking ATM. A pre-assembled DJβ complex that decreases the number of TCRβ rearrangements needed for a productive TCRβ gene further increased frequencies of ATM-deficient cells with bi-allelic TCRβ expression. IgH and TCRβ proteins drive proliferation of pro-lymphocytes through Cyclin D3, which also inhibits VH transcription. We show that inactivation of Cyclin D3 leads to increased frequencies of lymphocytes with bi-allelic expression of IgH or TCRβ genes. We also show that Cyclin D3 inactivation cooperates with ATM deficiency to increase the frequencies of cells with bi-allelic TCRβ or IgH expression, while decreasing the frequency of ATM-deficient lymphocytes with aberrant V-to-DJ recombination. Our data demonstrate that core components of the DNA damage response and cell cycle machinery cooperate to help enforce IgH and TCRβ allelic exclusion, and indicate that control of V-to-DJ rearrangements between alleles is important to maintain genomic stability.
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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：
29.7
作者：
Helmink BA;Sleckman BP
通讯作者：
Sleckman BP
DOI：
10.1084/jem.20061918
发表时间：
2007-01-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Casellas R;Zhang Q;Zheng NY;Mathias MD;Smith K;Wilson PC
通讯作者：
Wilson PC
影响因子：
4.4
作者：
Barreto, V;Cumano, A
通讯作者：
Cumano, A
影响因子：
5.1
作者：
AMMANN, AJ;HONG, R
通讯作者：
HONG, R