Aberrant replication timing induces defective chromosome condensation in Drosophila ORC2 mutants
Aberrant replication timing induces defective chromosome condensation in Drosophila ORC2 mutants
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DOI：
10.1016/s0960-9822(00)00844-7
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发表时间：
2000-12-14
期刊：
影响因子：
9.2
通讯作者：
Heck, MMS
中科院分区：
文献类型：
--
作者：
Loupart, ML;Krause, SA;Heck, MMS
背景：基因组的精确复制和包装是有丝分裂中染色体分离的绝对先决条件。为了进一步了解细胞周期染色体动力学的过程，我们对影响后生动物有丝分裂染色体浓缩的突变进行了首次详细表征。我们在果蝇中结合遗传和细胞学方法，补充并扩展了利用酵母遗传学和非洲爪蟾体外提取系统来表征高阶染色体结构和功能的现有工作。结果：发现 ORC2 基因的两个等位基因会导致幼虫发育后期死亡，并伴有细胞周期进展缺陷（S 期进入和中期退出延迟）和有丝分裂中染色体浓缩。在野生型细胞的 S 期进展过程中，常染色质复制较早，异染色质复制较晚。两个等位基因都破坏了染色体复制的正常模式，一些常染色质区域的复制甚至晚于异染色质。有丝分裂染色体不规则浓缩，常染色质的异常晚期复制区域在有丝分裂浓缩中表现出最大的问题。结论：结果不仅揭示了ORC2在后生动物染色体结构中的新功能，还表明DNA复制的正确时机可能对于完全能够进行有丝分裂浓缩的染色质组装至关重要。
Background: The accurate duplication and packaging of the genome is an absolute prerequisite to the segregation of chromosomes in mitosis. To understand the process of cell-cycle chromosome dynamics further, we have performed the first detailed characterization of a mutation affecting mitotic chromosome condensation in a metazoan. Our combined genetic and cytological approaches in Drosophila complement and extend existing work employing yeast genetics and Xenopus in vitro extract systems to characterize higher-order chromosome structure and function.Results: Two alleles of the ORC2 gene were found to cause death late in larval development, with defects in cell-cycle progression (delays in S-phase entry and metaphase exit) and chromosome condensation in mitosis. During S-phase progression in wild-type cells, euchromatin replicates early and heterochromatin replicates late. Both alleles disrupted the normal pattern of chromosomal replication, with some euchromatic regions replicating even later than heterochromatin. Mitotic chromosomes were irregularly condensed, with the abnormally late replicating regions of euchromatin exhibiting the greatest problems in mitotic condensation.Conclusions: The results not only reveal novel functions for ORC2 in chromosome architecture in metazoans, they also suggest that the correct timing of DNA replication may be essential for the assembly of chromatin that is fully competent to undergo mitotic condensation.