Novel roles of HP1a and Mcm10 in DNA replication, genome maintenance and photoreceptor cell differentiation.
Novel roles of HP1a and Mcm10 in DNA replication, genome maintenance and photoreceptor cell differentiation.
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DOI：
10.1093/nar/gkw1174
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发表时间：
2017-02-17
影响因子：
14.9
通讯作者：
Yamaguchi M
中科院分区：
文献类型：
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作者：
Vo N;Anh Suong DN;Yoshino N;Yoshida H;Cotterill S;Yamaguchi M
已知Mcm10和HP1a都是DNA复制所必需的。然而，其潜在的机制尚不清楚，尤其是对HP1。HP1a和Mcm10基因的敲除抑制了果蝇眼想象盘的S期进展。邻近连接分析表明，在S期，HP1a与包括Mcm10、RFC140和ε聚合酶255 kDa亚基在内的复制蛋白紧密相连。免疫共沉淀实验进一步证实了这一点。Mcm10和HP1a之间的PLA信号在有丝分裂周期细胞中特异观察到，而在内周期细胞中没有观察到。有趣的是，许多携带Mcm10和HP1a双重敲除的眼成像盘后部的细胞诱导了异位DNA合成和DNA损伤，但没有太多的异位凋亡。因此，G1-S检查点可能受到这两种蛋白敲除的影响。HP4和HP6等其他Hp家族蛋白也是如此。此外，Mcm10和HP1a都是光感受器细胞R1、R6和R7分化所必需的。对参与感光细胞分化的几个发育基因的进一步分析表明，这两种蛋白的作用都是通过调节菱形基因来调节的。
Both Mcm10 and HP1a are known to be required for DNA replication. However, underlying mechanism is not clarified yet especially for HP1. Knockdown of both HP1a and Mcm10 genes inhibited the progression of S phase in Drosophila eye imaginal discs. Proximity Ligation Assay (PLA) demonstrated that HP1a is in close proximity to DNA replication proteins including Mcm10, RFC140 and DNA polymerase ε 255 kDa subunit in S-phase. This was further confirmed by co-immunoprecipitation assay. The PLA signals between Mcm10 and HP1a are specifically observed in the mitotic cycling cells, but not in the endocycling cells. Interestingly, many cells in the posterior regions of eye imaginal discs carrying a double knockdown of Mcm10 and HP1a induced ectopic DNA synthesis and DNA damage without much of ectopic apoptosis. Therefore, the G1-S checkpoint may be affected by knockdown of both proteins. This event was also the case with other HP family proteins such as HP4 and HP6. In addition, both Mcm10 and HP1a are required for differentiation of photoreceptor cells R1, R6 and R7. Further analyses on several developmental genes involved in the photoreceptor cell differentiation suggest that a role of both proteins is mediated by regulation of the lozenge gene.
影响因子：
3.7
作者：
Vo N;Taga A;Inaba Y;Yoshida H;Cotterill S;Yamaguchi M
通讯作者：
Yamaguchi M