Drosophila Mxc protein is a component of the histone locus body (HLB), which is required for the expression of canonical histone genes, and severe mxc mutations generate tumors in larval hematopoietic tissues. A common characteristic of cancer cells is chromosomal instability (CIN), but whether mxc mutants exhibit this feature is unknown. Here, examination of post-meiotic spermatids created after male meiosis revealed that a fraction of the spermatids in hypomorphic mxcG46 mutants contained extra micronuclei or abnormally sized nuclei, corresponding to CIN. Moreover, we observed that the so-called lagging chromosomes retained between chromosomal masses separated toward spindle poles at telophase I. Time-lapse recordings show that micronuclei were generated from lagging chromosomes, and the abnormal chromosomes in mxcG46 mutants lacked centromeres. In normal spermatocyte nuclei, the HLB component FLASH colocalized with Mxc, whereas FLASH was dispersed in mxcG46 spermatocyte nuclei. Furthermore, we observed genetic interactions between Mxc and other HLB components in meiotic chromosome segregation, which suggests that inhibition of HLB formation is responsible for aberrant chromosome segregation in mxcG46. Quantitative real-time PCR revealed that canonical histone mRNA levels were decreased in mxcG46. Lastly, similar meiotic phenotypes appeared in the spermatids of histone H4 mutants and in the spermatids in testes depleted for chromosome-construction factors. Considering these genetic data, we propose that abnormal chromosome segregation leading to CIN development results from a loss of chromosome integrity caused by diminished canonical histone levels in mxc mutants.Key words: Chromosome instability, Drosophila, meiosis, tumor-suppressor gene.

中文翻译：

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mxc肿瘤抑制基因的突变导致果蝇雄性减数分裂中的染色体不稳定。

果蝇Mxc蛋白是组蛋白基因座体（HLB）的组成部分，它是规范性组蛋白基因表达所必需的，严重的mxc突变会在幼虫造血组织中产生肿瘤。癌细胞的共同特征是染色体不稳定性（CIN），但mxc突变体是否表现出此特征尚不清楚。在这里，检查雄性减数分裂后产生的减数分裂后的精子细胞，发现亚同型mxcG46突变体中一部分精子细胞含有额外的微核或异常大小的核，相当于CIN。此外，我们观察到所谓的滞后染色体保留在末期I处靠近纺锤极的染色体团之间。延时记录显示，滞后染色体产生了微核，而mxcG46突变体中的异常染色体缺少着丝粒。在正常的精母细胞核中，HLB组分FLASH与Mxc共定位，而FLASH分散在mxcG46精母细胞核中。此外，我们观察到Mxc与减数分裂染色体分离中其他HLB组件之间的遗传相互作用，这表明抑制HLB形成是mxcG46中异常染色体分离的原因。实时定量PCR分析表明，mxcG46中典型的组蛋白mRNA水平降低。最后，类似的减数分裂表型出现在组蛋白H4突变体的精子和睾丸中的精子中，这些精子减少了染色体构成因子。考虑到这些遗传数据，我们认为导致CIN发育的异常染色体分离是由mxc突变体中规范组蛋白水平降低引起的染色体完整性丧失造成的。