Rev3, the catalytic subunit of Polζ, is required for maintaining fragile site stability in human cells.
Rev3, the catalytic subunit of Polζ, is required for maintaining fragile site stability in human cells.
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DOI：
10.1093/nar/gks1442
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发表时间：
2013-02-01
影响因子：
14.9
通讯作者：
Xiao W
中科院分区：
文献类型：
--
作者：
Bhat A;Andersen PL;Qin Z;Xiao W
长期以来，人们一直推测哺乳动物的Rev3在哺乳动物的发育过程中扮演着一个重要而未知的角色(S)，因为Rev3的缺失会导致小鼠胚胎死亡，而到目前为止还没有研究过的其他跨损伤DNA合成聚合酶对小鼠胚胎发育是必需的。在这里，我们报告了POLζ的两个亚单位(Rev3和Rev7)在G2/M期表现出意外的表达增加，但它们独立地定位于有丝分裂细胞。实验缺失Rev3导致后期桥、染色体断裂/缺口和共同脆性部位(CFS)表达显著增加，而Rev7缺失主要导致落后的染色体缺陷，没有CFS表达的迹象。Rev3缺失引起的基因组不稳定性似乎与复制应激有关，因为用aphidiclin处理会进一步增强这种不稳定性，并导致中期特异的Fanconi贫血互补D2型(FANCD2)焦点形成增加，以及FANCD2阳性的后期桥。事实上，在培养的人类细胞中，Rev3的长期缺失会导致大量的基因组不稳定和严重的细胞周期停滞。上述观察结果共同支持这样一种观点，即Rev3是G2/M期CFSS有效复制所必需的，并且Rev3基因敲除小鼠所产生的脆性位点不稳定可能触发胚胎发育期间的细胞死亡。
It has been long speculated that mammalian Rev3 plays an important, yet unknown role(s) during mammalian development, as deletion of Rev3 causes embryonic lethality in mice, whereas no other translesion DNA synthesis polymerases studied to date are required for mouse embryo development. Here, we report that both subunits of Polζ (Rev3 and Rev7) show an unexpected increase in expression during G2/M phase, but they localize independently in mitotic cells. Experimental depletion of Rev3 results in a significant increase in anaphase bridges, chromosomal breaks/gaps and common fragile site (CFS) expression, whereas Rev7 depletion primarily causes lagging chromosome defect with no sign of CFS expression. The genomic instability induced by Rev3 depletion seems to be related to replication stress, as it is further enhanced on aphidicolin treatment and results in increased metaphase-specific Fanconi anemia complementation group D type 2 (FANCD2) foci formation, as well as FANCD2-positive anaphase bridges. Indeed, a long-term depletion of Rev3 in cultured human cells results in massive genomic instability and severe cell cycle arrest. The aforementioned observations collectively support a notion that Rev3 is required for the efficient replication of CFSs during G2/M phase, and that the resulting fragile site instability in Rev3 knockout mice may trigger cell death during embryonic development.
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影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
Bartek, J
影响因子：
64.5
作者：
Casper, AM;Nghiem, P;Glover, TW
通讯作者：
Glover, TW
DOI：
10.1084/jem.20050292
发表时间：
2005-04-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Delbos F;De Smet A;Faili A;Aoufouchi S;Weill JC;Reynaud CA
通讯作者：
Reynaud CA
影响因子：
5.3
作者：
Hicks, J. Kevin;Chute, Colleen L.;Canman, Christine E.
通讯作者：
Canman, Christine E.
影响因子：
21.3
作者：
Chan, Kok Lung;Palmai-Pallag, Timea;Hickson, Ian D.
通讯作者：
Hickson, Ian D.