Rearrangements of the MLL gene are influenced by DNA secondary structure, potentially mediated by topoisomerase II binding.
Rearrangements of the MLL gene are influenced by DNA secondary structure, potentially mediated by topoisomerase II binding.
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DOI：
10.1002/gcc.20685
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发表时间：
2009-09
影响因子：
3.7
通讯作者：
Vaughan, Andrew T.
中科院分区：
文献类型：
--
作者：
Le, Hongan;Singh, Sheetal;Shih, Shyh-Jen;Du, Nga;Schnyder, Sabine;Loredo, Grace A.;Bien, Christine;Michaelis, Laura;Toor, Arnir;Diaz, Manuel O.;Vaughan, Andrew T.
与靶向拓扑异构酶II的药物相关的治疗相关急性髓细胞白血病和婴儿急性白血病（IAL）中MLL易位断裂点的位置偏向于MLL的内含子11 -外显子12区域，但缺乏全面的解释。为了解决这个问题，从接受拓扑异构酶II抑制剂治疗的乳腺癌和淋巴瘤患者中采集血液样品。反向PCR分析用于询问MLL的外显子12区域的重排。观察到的19个易位中有11个显示断点连接仅限于外显子12内的单个5 bp位置。在暴露于雌激素（与IAL相关）或抗CD 95抗体的TK 6细胞中观察到类似的限制性分布（11/20个断点连接）。易位热点位于10 bp片段的5'端，与101 bp的完全回文序列相匹配。在回文间的几何中点处注意到高严格性拓扑异构酶II共有序列结合位点。使用连接介导的PCR筛选暴露于抗CD 95抗体的TK 6细胞，发现14/37（38%）的DNA断裂位于5'回文序列附近，10/37（27%）位于3'配偶体。我们提出了一个模型，拓扑异构酶II有利于组织核酸酶敏感的二级结构，稳定的回文关联，这是容易重排。
The location of MLL translocation breakpoints within therapy-related acute myeloid leukemia linked to drugs targeting Topoisomerase II and infant acute leukemia (IAL) are biased towards the intron 11 - exon 12 region of MLL, though lacking a comprehensive explanation. To address this, blood samples were taken from breast cancer and lymphoma patients receiving Topoisomerase II inhibitor therapy. Inverse PCR analysis was used to interrogate the exon 12 region of MLL for rearrangements. Eleven of 19 observed translocations showed breakpoint junctions restricted to a single 5 bp location within exon 12. A similarly restricted distribution (11/20 breakpoint junctions) was observed in TK6 cells exposed to either estrogen (linked to IAL) or anti-CD95 antibody. The translocation hotspot was at the 5' edge of a 10 bp tract matched with a perfect palindrome, 101 bp distant. A high stringency Topoisomerase II consensus sequence binding site was noted at the geometric midpoint between palindromes. Using ligation-mediated PCR to screen TK6 cells exposed to anti-CD95 antibody showed 14/37 (38%) of DNA breaks were found adjacent to the 5' palindrome and 10/37 (27%) at the 3' partner. We propose a model whereby Topoisomerase II facilitates the organization of nuclease sensitive secondary structures, stabilized by palindrome association, which are prone to rearrangement.
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影响因子：
9.8
作者：
Mirault, Marc-Edouard;Boucher, Patrick;Tremblay, Alain
通讯作者：
Tremblay, Alain
影响因子：
64.8
作者：
Dong, Ken C.;Berger, James M.
通讯作者：
Berger, James M.
DOI：
10.1073/pnas.171309898
发表时间：
2001-08-14
影响因子：
11.1
作者：
Lovett, BD;Lo Nigro, L;Felix, CA
通讯作者：
Felix, CA
DOI：
10.1073/pnas.061029098
发表时间：
2001-03-13
影响因子：
11.1
作者：
Vologodskii, AV;Zhang, WT;Cozzarelli, NR
通讯作者：
Cozzarelli, NR
影响因子：
11.4
作者：
Betti, CJ;Villalobos, MJ;Vaughan, ATM
通讯作者：
Vaughan, ATM