Interstrand crosslink-induced radials form between non-homologous chromosomes, but are absent in sex chromosomes
Interstrand crosslink-induced radials form between non-homologous chromosomes, but are absent in sex chromosomes
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DOI：
10.1016/j.dnarep.2004.01.011
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发表时间：
2004-05-04
期刊：
影响因子：
3.8
通讯作者：
Olson, SB
中科院分区：
文献类型：
--
作者：
Newell, AEH;Akkari, YMN;Olson, SB
Fanconi贫血（FA）和缺乏功能性BRCA 1和BRCA 2蛋白的细胞对链间交联（ICL）试剂过敏，并显示染色体断裂和放射性数量增加。虽然放射状地层已被用于诊断FA超过30年，有这些特征的地层分析很少。在本研究中，分析了FA-A和FA-G成纤维细胞以及用高剂量ICL处理的正常和逆转录病毒校正的FA-A成纤维细胞的放射状。辐射被发现只涉及非同源染色体的相互作用，并几乎随机分布沿着染色体的长度。染色体上确实显示放射状受累频率增加的位点与已知的脆性位点或臂旁区域无关。在通过微细胞介导的小鼠染色体转移到人FA-A成纤维细胞中产生的人-小鼠杂交细胞中，观察到小鼠和人染色体之间的杂交辐射。X和Y染色体均不参与辐状体的形成。这些观察结果表明，ICL修复可能涉及短的同源性，导致异常的放射状形成在FA蛋白的情况下。(C)2004 Elsevier B. V.保留所有权利。
Fanconi anemia (FA) and cells lacking functional BRCA1 and BRCA2 proteins are hypersensitive to interstrand crosslinking (ICL) agents and show increased numbers of chromosomal breaks and radials. Although radial formation has been used to diagnose FA for more than 30 years, there has been little analysis of these characteristic formations. In this study, radials were analyzed from FA-A and FA-G fibroblasts as well as normal and retrovirally-corrected FA-A fibroblasts treated with high doses of ICLs. Radials were found to only involve non-homologous chromosome interactions and to be distributed nearly randomly along the length of chromosomes. Sites on chromosomes that did show increased frequency of radial involvement did not correlate with known fragile sites or pericentric regions. Hybrid radials were observed between mouse and human chromosomes in human-mouse hybrid cells produced by microcell-mediated chromosome transfer of mouse chromosomes into human FA-A fibroblasts. Both X and Y chromosomes were notably not involved in radials. These observations suggest that ICL repair may involve short stretches of homology, resulting in aberrant radial formation in the absence of FA proteins. (C) 2004 Elsevier B.V. All rights reserved.