Repression of mutagenesis by Rad51D-mediated homologous recombination.
Repression of mutagenesis by Rad51D-mediated homologous recombination.
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DOI：
10.1093/nar/gkl020
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发表时间：
2006
影响因子：
14.9
通讯作者：
Thompson LH
中科院分区：
文献类型：
--
作者：
Hinz JM;Tebbs RS;Wilson PF;Nham PB;Salazar EP;Nagasawa H;Urbin SS;Bedford JS;Thompson LH
同源重组修复（HRR）修复DNA复制过程中出现的染色单体断裂，并防止可能发生的染色体重排，从这种断裂的错误修复。在脊椎动物中，五个Rad 51旁系同源物被确定为以非必需但关键的方式对HRR熟练度做出贡献。我们构建并表征了在广泛研究的CHO细胞中敲除parabolic Rad 51 D。rad 51 d突变体（克隆51 D1）对多种诱导DNA损伤谱（包括γ射线、紫外线（UV）-C辐射和甲磺酸甲酯（MMS））表现出敏感性，表明HRR与遗传毒性的广泛相关性。自发染色单体断裂/间隙和等染色单体断裂升高3- 12倍，但染色体数目分布保持不变。最重要的是，51 D1细胞表现出12倍的hprt突变率增加，以及4至10倍的dhfr和CAD基因座的基因扩增率分别增加。来自相同亲本CHO系的Xrcc 3 irs 1 SF细胞在这三个基因座处显示类似的升高的诱变。总的来说，这些结果证实了HRR以无错误的方式抑制三类遗传改变（染色体畸变、基因功能丧失和基因表达增加）的先验预期，所有这些都与致癌作用相关。
Homologous recombinational repair (HRR) restores chromatid breaks arising during DNA replication and prevents chromosomal rearrangements that can occur from the misrepair of such breaks. In vertebrates, five Rad51 paralogs are identified that contribute in a nonessential but critical manner to HRR proficiency. We constructed and characterized a knockout of the paralog Rad51D in widely studied CHO cells. The rad51d mutant (clone 51D1) displays sensitivity to a diverse spectrum of induced DNA damage including γ-rays, ultraviolet (UV)-C radiation, and methyl methanesulfonate (MMS), indicating the broad relevance of HRR to genotoxicity. Spontaneous chromatid breaks/gaps and isochromatid breaks are elevated 3- to 12-fold, but the chromosome number distribution remains unchanged. Most importantly, 51D1 cells exhibit a 12-fold-increased rate of hprt mutation, as well as 4- to 10-fold increased rates of gene amplification at the dhfr and CAD loci, respectively. Xrcc3 irs1SF cells from the same parental CHO line show similarly elevated mutagenesis at these three loci. Collectively, these results confirm the a priori expectation that HRR acts in an error-free manner to repress three classes of genetic alterations (chromosomal aberrations, loss of gene function and increased gene expression), all of which are associated with carcinogenesis.
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DOI：
10.1016/0027-5107(87)90030-3
发表时间：
1987-03-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
DARROUDI, F;NATARAJAN, AT
通讯作者：
NATARAJAN, AT
DOI：
10.1016/s0027-5107(99)00091-3
发表时间：
1999-06-30
影响因子：
2.3
作者：
Glaab, WE;Tindall, KR;Skopek, TR
通讯作者：
Skopek, TR
影响因子：
2.5
作者：
Hakem, R;de la Pompa, JL;Mak, TW
通讯作者：
Mak, TW
影响因子：
2.7
作者：
Kraakman-van der Zwet, M;Wiegant, WW;Zdzienicka, MZ
通讯作者：
Zdzienicka, MZ
影响因子：
5.3
作者：
Lundin, C;Erixon, K;Helleday, T
通讯作者：
Helleday, T