Drosophila timeless2 Is Required for Chromosome Stability and Circadian Photoreception
Drosophila timeless2 Is Required for Chromosome Stability and Circadian Photoreception
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DOI：
10.1016/j.cub.2009.12.048
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发表时间：
2010-02-23
期刊：
影响因子：
9.2
通讯作者：
Sandrelli, Federica
中科院分区：
文献类型：
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作者：
Benna, Clara;Bonaccorsi, Silvia;Sandrelli, Federica
在果蝇中，有两个永恒的对应物，无时间1(Tim1)和无时间2(tim2，或超时)[1，2]。系统发育分析表明，tim1起源于寒武纪爆发前后tim2的复制[3]。作为典型的昼夜节律成分，tim1的功能已经得到很好的证实[4]，但tim2在果蝇中的作用却鲜为人知。许多生物拥有单一的类似tim2的基因，该基因与DNA合成有关，对于哺乳动物来说，有些争议的是，它与昼夜节律有关[2，5]。在这里，我们分析了Fly tim2的结构和功能。Tim2是一个大的基因座(类似于75kb)，它含有几个转录的内含子序列。利用插入突变和组织特异性RNA干扰介导的下调，我们发现tim2是正常DNA代谢和染色体完整性所必需的基因。此外，Tim2通过其在视叶T1篮子细胞中的表达，参与成人昼夜节律时钟的光携带。因此，Tim2‘S在光夹带中的残留作用提供了一种进化联系，可以解释为什么它的派生准对数Tim1在昼夜光敏性和核心时钟功能中都扮演着如此重要的角色。
In Drosophila, there are two timeless paralogs, timelessl (tim1) and timeless2 (tim2, or timeout) [1, 2]. Phylogenetic analyses suggest that tim1 originated as a duplication of tim2 around the time of the Cambrian explosion [3]. The function of tim1 as a canonical circadian component is well established [4], but the role of tim2 in the fly is poorly understood. Many organisms possess a single tim2-like gene that has been implicated in DNA synthesis and, in the case of mammals, somewhat controversially, in circadian rhythmicity [2, 5]. Here we analyze the structure and the functional role of fly tim2. tim2 is a large locus (similar to 75 kb) that harbors several transcribed intronic sequences. Using insertional mutations and tissue-specific RNA interference-mediated downregulation, we find that tim2 is an essential gene required for normal DNA metabolism and chromosome integrity. Moreover, tim2 is involved in light entrainment of the adult circadian clock, via its expression in the T1 basket cells of the optic lobes. tim2's residual role in light entrainment thus provides an evolutionary link that may explain why its derived paralog, tim1, came to play such a major role in both circadian photosensitivity and core clock function.