RRC ID 59100
著者 Tanabe K, Awane R, Shoda T, Yamazoe K, Inoue YH.
タイトル Mutations in mxc Tumor-Suppressor Gene Induce Chromosome Instability in Drosophila Male Meiosis.
ジャーナル Cell Struct Funct
Abstract 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.
巻・号 44(2)
ページ 121-135
公開日 2019-10-23
DOI 10.1247/csf.19022
PMID 31484839
MeSH Animals Chromosomal Instability* Chromosomes, Insect / genetics* Drosophila / cytology* Drosophila / genetics* Drosophila Proteins / genetics* Drosophila Proteins / metabolism Male Meiosis / genetics* Mutation* Tumor Suppressor Proteins / genetics* Tumor Suppressor Proteins / metabolism
IF 2.429
引用数 2
リソース情報
ショウジョウバエ DGRC#150122