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DNA mismatches and GC-rich motifs target transposition by the RAG1/RAG2 transposase.DNA错配和富含GC的基序通过RAG1/RAG2转座酶靶向转座。
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V(D)J recombination: RAG proteins, repair factors, and regulation.V(D)J重排:RAG蛋白、修复因子与调控
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由于V(D)J重组相关转座导致的基因组不稳定。

Genomic instability due to V(D)J recombination-associated transposition.

作者信息

Reddy Yeturu V R, Perkins Eric J, Ramsden Dale A

机构信息

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

出版信息

Genes Dev. 2006 Jun 15;20(12):1575-82. doi: 10.1101/gad.1432706.

DOI:10.1101/gad.1432706
PMID:16778076
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1482478/
Abstract

The first step in assembling immunoglobulin and T-cell receptors by V(D)J recombination has similarities to transposon excision. The excised transposon-like element then integrates into DNA targets at random in vitro, but whether this activity significantly threatens the genomic integrity of its host has been unclear. Here, we recover examples where the putative transposon associated with V(D)J recombination integrated into the genome of a pre-B-cell line. Transposition accounted for a surprisingly high proportion (one-third) of integrations, while most of the remaining events had parallels to other aberrant V(D)J recombination pathways linked to oncogenic translocation. In total, transposition occurred approximately once every 50,000 V(D)J recombinations. Transposition may thus contribute significantly to genomic instability.

摘要

通过V(D)J重排组装免疫球蛋白和T细胞受体的第一步与转座子切除有相似之处。然后,切除的类转座子元件在体外随机整合到DNA靶点中,但这种活性是否会对其宿主的基因组完整性构成重大威胁尚不清楚。在这里,我们找到了一些例子,其中与V(D)J重排相关的假定转座子整合到了一个前B细胞系的基因组中。转座在整合事件中占比惊人地高(三分之一),而其余大多数事件与其他与致癌易位相关的异常V(D)J重排途径相似。总体而言,每50000次V(D)J重排中大约发生一次转座。因此,转座可能对基因组不稳定性有重大影响。