Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities.
Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities.
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I型和II型拓扑异构酶的细胞周期耦合搬迁以及催化酶活性的调节。
DOI：
10.1083/jcb.136.4.775
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发表时间：
1997-02-24
影响因子：
7.8
通讯作者：
Boege, F
中科院分区：
文献类型：
--
作者：
Meyer, KN;Kjeldsen, E;Straub, T;Knudsen, BR;Hickson, ID;Kikuchi, A;Kreipe, H;Boege, F
我们可视化的DNA拓扑异构酶在A431细胞和分离染色体的同工酶选择性免疫荧光显微镜。在间期，拓扑异构酶I主要分布在核内。10 - 15%的细胞呈颗粒状，30%的细胞呈明亮的核仁内斑。拓扑异构酶Ⅱ同工酶在整个间期内呈斑点状（α）或网状（β）核型。与拓扑异构酶II α相反，拓扑异构酶II β完全被排除在核仁之外。在有丝分裂中，拓扑异构酶II β完全扩散到胞质溶胶中，而拓扑异构酶I和II α保持染色体结合。拓扑异构酶I的染色是均匀的，而拓扑异构酶II α聚集在染色体臂的长轴和中心粒中。拓扑异构酶抗原在有丝分裂期比间期高2 - 3倍，但拓扑异构酶I和II的比活性分别降低5倍和2.4倍。这些变化与有丝分裂酶过度磷酸化有关。在分裂间期，拓扑异构酶II α可被依托泊苷或喜树碱完全连接到DNA上，而在有丝分裂期，有50%的拓扑异构酶II α逃脱了中毒。对依托泊苷的不耐受性可归因于拓扑异构酶II α的盐稳定支架部分，其从G1期的<2%增加到有丝分裂期的48%。拓扑异构酶I和II β在整个细胞周期中保持完全可提取。总之，拓扑异构酶的表达增加有丝分裂，但比活性下降。拓扑异构酶II β从异染色质释放，而拓扑异构酶I和II α保持染色体结合。支架相关拓扑异构酶II α似乎不参与催化DNA周转，但它可能在中心粒的复制周期中发挥作用，在M期积累。
We visualized DNA topoisomerases in A431 cells and isolated chromosomes by isoenzyme-selective immunofluorescence microscopy. In interphase, topoisomerase I mainly had a homogeneous nuclear distribution. 10–15% of the cells exhibited granular patterns, 30% showed bright intranucleolar patches. Topoisomerase II isoenzymes showed spotted (α) or reticular (β) nuclear patterns throughout interphase. In contrast to topoisomerase IIα, topoisomerase IIβ was completely excluded from nucleoli. In mitosis, topoisomerase IIβ diffused completely into the cytosol, whereas topoisomerases I and IIα remained chromosome bound. Chromosomal staining of topoisomerase I was homogeneous, whereas topoisomerase IIα accumulated in the long axes of the chromosome arms and in the centriols. Topoisomerase antigens were 2–3-fold higher in mitosis than in interphase, but specific activities of topoisomerase I and II were reduced 5- and 2.4-fold, respectively. These changes were associated with mitotic enzyme hyperphosphorylation. In interphase, topoisomerases could be completely linked to DNA by etoposide or camptothecin, whereas in mitosis, 50% of topoisomerase IIα escaped poisoning. Refractoriness to etoposide could be assigned to the salt-stable scaffold fraction of topoisomerase IIα, which increased from <2% in G1 phase to 48% in mitosis. Topoisomerases I and IIβ remained completely extractable throughout the cell cycle. In summary, expression of topoisomerases increases towards mitosis, but specific activities decrease. Topoisomerase IIβ is released from the heterochromatin, whereas topoisomerase I and IIα remain chromosome bound. Scaffold-associated topoisomerase IIα appears not to be involved in catalytic DNA turnover, though it may play a role in the replicational cycle of centriols, where it accumulates during M phase.
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影响因子：
4.8
作者：
Boege, F;Straub, T;Kohrle, J
通讯作者：
Kohrle, J
影响因子：
4.8
作者：
Kimura, K;Nozaki, N;Kikuchi, A
通讯作者：
Kikuchi, A
DOI：
10.1073/pnas.90.24.11508
发表时间：
1993-12-15
影响因子：
11.1
作者：
KRETZSCHMAR, M;MEISTERERNST, M;ROEDER, RG
通讯作者：
ROEDER, RG
影响因子：
19
作者：
Lange, BMH;Gull, K
通讯作者：
Gull, K
拓扑异构酶II在有丝分裂染色体中的定位。
影响因子：
7.8
作者：
Earnshaw, W C;Heck, M M
通讯作者：
Heck, M M