Similar effects of BRCA2 truncation and Rad51 paralog deficiency on immunoglobulin V gene diversification in DT40 cells support an early role for Rad51 paralogs in homologous recombination
Similar effects of BRCA2 truncation and Rad51 paralog deficiency on immunoglobulin V gene diversification in DT40 cells support an early role for Rad51 paralogs in homologous recombination
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DOI：
10.1128/mcb.25.3.1124-1134.2005
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发表时间：
2005-02-01
影响因子：
5.3
通讯作者：
Takeda, S
中科院分区：
文献类型：
--
作者：
Hatanaka, A;Yamazoe, M;Takeda, S
BRCA2是一种与遗传性乳腺癌和卵巢癌相关的肿瘤抑制基因。虽然Brca2蛋白参与同源DNA重组（HR），但其确切作用仍不清楚。从鸡DT 40细胞中，我们产生了BRCA 2基因缺陷细胞，其在BRC3重复序列的3'端具有截短（brca2tr）。比较brca2tr细胞与其他HR缺陷型DT 40克隆的特征，发现它们与rad51 Parkinson突变体（rad51 b、rad51 c、rad51 d、xrcc 2或xrcc 3细胞）具有显著的相似性。表型相似性包括从HR介导的多样化到免疫球蛋白可变基因片段中的单核苷酸取代的转变，以及通过Rad51的过表达对这种转变的部分逆转。虽然最近的证据支持至少Xrcc 3和Rad51C在HR后期发挥作用，但我们的数据表明，Brca 2和Rad51旁系同源物也可能在同一早期步骤对HR起作用，它们的丢失导致刺激另一种易出错的修复途径。
BRCA2 is a tumor suppressor gene that is linked to hereditary breast and ovarian cancer. Although the Brca2 protein participates in homologous DNA recombination (HR), its precise role remains unclear. From chicken DT40 cells, we generated BRCA2 gene-deficient cells which harbor a truncation at the 3' end of the BRC3 repeat (brca2tr). Comparison of the characteristics of brca2tr cells with those of other HR-deficient DT40 clones revealed marked similarities with rad51 paralog mutants (rad51b, rad51c, rad51d, xrcc2, or xrcc3 cells). The phenotypic similarities include a shift from HR-mediated diversification to single-nucleotide substitutions in the immunoglobulin variable gene segment and the partial reversion of this shift by overexpression of Rad51. Although recent evidence supports at least Xrcc3 and Rad51C playing a role late in HR, our data suggest that Brca2 and the Rad51 paralogs may also contribute to HR at the same early step, with their loss resulting in the stimulation of an alternative, error-prone repair pathway.