Direct Regulation of DNA Repair by E2F and RB in Mammals and Plants: Core Function or Convergent Evolution?

Direct Regulation of DNA Repair by E2F and RB in Mammals and Plants: Core Function or Convergent Evolution?
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DOI:
10.3390/cancers13050934
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发表时间:
2021-02-24
期刊:
影响因子:
5.2
通讯作者:
Johnson DG
Johnson DG
中科院分区:
医学2区
文献类型:
--
作者:
Manickavinayaham S;Dennehey BK;Johnson DG

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在许多真核生物中,视网膜母细胞瘤(Retinoblastoma, RB)蛋白和E2F转录因子共同调控细胞周期。在缺乏其中一种或两种蛋白质的生物体中,其他蛋白质承担了细胞周期调节的基本功能。RB和E2F在细胞周期外也有重要的功能,包括DNA修复。这篇综述总结了RB和E2F在维持基因组完整性方面的非规范功能,并提出了这样的功能是一直存在还是最近才进化出来的问题。在大多数真核生物中,E2F转录因子家族的成员调节DNA复制和有丝分裂细胞分裂的重要基因的表达。视网膜母细胞瘤(RB)肿瘤抑制因子的同源物抑制E2F因子的活性,从而控制细胞周期的进展。诸如出芽酵母和裂变酵母等生物体失去了编码E2F和RB的基因,但获得了编码其他蛋白质的基因,这些蛋白质承担E2F和RB细胞周期相关功能。除了调节细胞增殖外,E2F和RB同源物在多种真核生物有丝分裂细胞周期外具有非规范功能。例如,在哺乳动物和植物中,E2F和RB同源物定位于DNA双链断裂(DSBs),并通过同源重组(HR)直接促进修复。在这里,我们讨论了哺乳动物E2F1和RB及其拟南芥同源物E2FA和RB相关(RBR)之间的相似之处,包括它们在DNA损伤位点的招募以及它们如何帮助招募对DNA末端切除重要的修复因子。我们还探讨了DNA修复中的这种作用是E2F和RB同源物在最后真核生物共同祖先中的保守古老功能,还是这种功能在哺乳动物和植物中独立进化的问题。
Retinoblastoma (RB) proteins and E2F transcription factors partner together to regulate the cell cycle in many eukaryotic organisms. In organisms that lack one or both of these proteins, other proteins have taken on the essential function of cell cycle regulation. RB and E2F also have important functions outside of the cell cycle, including DNA repair. This review summarizes the non-canonical functions of RB and E2F in maintaining genome integrity and raises the question of whether such functions have always been present or have evolved more recently. Members of the E2F transcription factor family regulate the expression of genes important for DNA replication and mitotic cell division in most eukaryotes. Homologs of the retinoblastoma (RB) tumor suppressor inhibit the activity of E2F factors, thus controlling cell cycle progression. Organisms such as budding and fission yeast have lost genes encoding E2F and RB, but have gained genes encoding other proteins that take on E2F and RB cell cycle-related functions. In addition to regulating cell proliferation, E2F and RB homologs have non-canonical functions outside the mitotic cell cycle in a variety of eukaryotes. For example, in both mammals and plants, E2F and RB homologs localize to DNA double-strand breaks (DSBs) and directly promote repair by homologous recombination (HR). Here, we discuss the parallels between mammalian E2F1 and RB and their Arabidopsis homologs, E2FA and RB-related (RBR), with respect to their recruitment to sites of DNA damage and how they help recruit repair factors important for DNA end resection. We also explore the question of whether this role in DNA repair is a conserved ancient function of the E2F and RB homologs in the last eukaryotic common ancestor or whether this function evolved independently in mammals and plants.
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