Depletion of the mini-chromosome maintenance complex binding protein allows the progression of cytokinesis despite abnormal karyokinesis during the asexual development of Plasmodium falciparum.
Depletion of the mini-chromosome maintenance complex binding protein allows the progression of cytokinesis despite abnormal karyokinesis during the asexual development of Plasmodium falciparum.
复制标题
在恶性疟原虫无性发育过程中，尽管核分裂异常，但小染色体维持复合体结合蛋白的耗竭允许细胞分裂的进展。
DOI：
10.1111/cmi.13284
复制
发表时间：
2021-03
影响因子：
3.4
通讯作者：
Dvorin JD
中科院分区：
文献类型：
--
作者：
Absalon S;Dvorin JD
真核细胞周期通常分为不同的阶段，有丝分裂后立即有胞质分裂。为了确保正确的细胞分裂，每个阶段都通过称为检查点的反馈控制进行紧密协调。在其无性复制周期中，恶性疟原虫（Plasmodium falciparum）经历多个异步轮的有丝分裂，伴随着未浓缩染色体的分离，随后是具有完整核膜的核分裂。然后，多核裂殖体经历一轮胞质分裂，产生数十个子细胞，称为裂殖子。迄今为止，没有细胞周期检查点已被确定为调节疟原虫属。分裂模式。在这里，我们确定了疟原虫同源的微型染色体维护复合物结合蛋白（PfMCMBP），共纯化的微型染色体维护（MCM）复杂，基因组DNA复制所需的复制解旋酶。通过有条件地消耗PfMCMBP，我们破坏核形态和寄生虫增殖，而不会导致DNA复制的阻断。通过免疫荧光显微镜，我们发现PfMCMBP耗竭促进有丝分裂纺锤体微管的形成，并延伸到一个以上的DNA焦点和异常的中心蛋白分布。引人注目的是，PfMCMBP缺陷型寄生虫完成胞质分裂并形成具有可变细胞和核大小的非整倍体裂殖子。我们的研究表明，寄生虫缺乏一个强大的检查点反应，以防止胞质分裂后异常核分裂。
The eukaryotic cell cycle is typically divided into distinct phases with cytokinesis immediately following mitosis. To ensure proper cell division, each phase is tightly coordinated via feedback controls named checkpoints. During its asexual replication cycle, the malaria parasite Plasmodium falciparum undergoes multiple asynchronous rounds of mitosis with segregation of uncondensed chromosomes followed by nuclear division with intact nuclear envelope. The multi-nucleated schizont is then subjected to a single round of cytokinesis that produces dozens of daughter cells called merozoites. To date, no cell cycle checkpoints have been identified that regulate the Plasmodium spp. mode of division. Here, we identify the Plasmodium homologue of the Mini-Chromosome Maintenance Complex Binding Protein (PfMCMBP), which co-purified with the Mini-Chromosome Maintenance (MCM) complex, a replicative helicase required for genomic DNA replication. By conditionally depleting PfMCMBP, we disrupt nuclear morphology and parasite proliferation without causing a block in DNA replication. By immunofluorescence microscopy, we show that PfMCMBP depletion promotes the formation of mitotic spindle microtubules with extensions to more than one DNA focus and abnormal centrin distribution. Strikingly, PfMCMBP-deficient parasites complete cytokinesis and form aneuploid merozoites with variable cellular and nuclear sizes. Our study demonstrates that the parasite lacks a robust checkpoint response to prevent cytokinesis following aberrant karyokinesis.
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DOI：
10.1038/nrm3494
发表时间：
2013-01
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Mitchell AL;Attwood TK;Babbitt PC;Blum M;Bork P;Bridge A;Brown SD;Chang HY;El-Gebali S;Fraser MI;Gough J;Haft DR;Huang H;Letunic I;Lopez R;Luciani A;Madeira F;Marchler-Bauer A;Mi H;Natale DA;Necci M;Nuka G;Orengo C;Pandurangan AP;Paysan-Lafosse T;Pesseat S;Potter SC;Qureshi MA;Rawlings ND;Redaschi N;Richardson LJ;Rivoire C;Salazar GA;Sangrador-Vegas A;Sigrist CJA;Sillitoe I;Sutton GG;Thanki N;Thomas PD;Tosatto SCE;Yong SY;Finn RD
通讯作者：
Finn RD
影响因子：
6.7
作者：
Collins CR;Hackett F;Strath M;Penzo M;Withers-Martinez C;Baker DA;Blackman MJ
通讯作者：
Blackman MJ
影响因子：
1.5
作者：
Patterson, S;Robert, C;Chakrabarti, D
通讯作者：
Chakrabarti, D
DOI：
10.1073/pnas.1619441114
发表时间：
2017-03-28
影响因子：
11.1
作者：
Hale, Victoria L.;Watermeyer, Jean M.;Saibil, Helen R.
通讯作者：
Saibil, Helen R.