Function of RecQ helicases in genome stability

在人类中有五个RecQ解旋酶，而在更简单的生物体中只有一个。 探索这些RecQ解旋酶如何单独和一起发挥作用以及解旋酶功能是否存在缺失或每个解旋酶是否发挥单独的作用是非常有趣的。 可能存在它们可以以协同方式起作用的情况，并且这将提供关于这些不同RecQ解旋酶是否彼此相互作用以及关于某些过程的生物学重要性的信息。 我们和其他研究小组发现，人类RecQ解旋酶参与DNA修复，更具体地说，参与DNA修复的某些子途径。 RecQ解旋酶中的三种在过早衰老的病症中缺乏：Werner综合征、Bloom综合征和Rothmund Thomson综合征。 关于Rothmund-Thomson综合征蛋白RECQ 4和RecQ 5的了解比其他人类RecQ解旋酶少得多。 我们发现RecQ 4蛋白参与双链和单链断裂的DNA修复，并且患有这种疾病的个体的细胞在DNA修复中存在缺陷。在生物化学上，我们正在表征RECQ 4蛋白，虽然其解旋酶功能在许多方面与WRN和BLM解旋酶相似，但也存在显着差异。 此外，我们目前正在探索RECQ 4参与的蛋白质相互作用和蛋白质复合物的潜力。 RecQ 5是RecQ家族的另一个成员，其信息很少。我们以前报道过WRN、BLM和RecQ 4可以刺激核心碱基切除修复蛋白。因此，我们正在评估RecQ 5是否也可以刺激BER蛋白并与之相互作用。

In humans there are five RecQ helicases whereas in simpler organisms there are only one. It is of great interest to explore how these RecQ helicases function individually and together and whether there is abundancy of helicase function or whether each play an individual role. There may be circumstances where they can function in a synergistic manner and this would be informative about whether these different RecQ helicases interact with each other and also about the biological importance of certain processes. We and other groups find that the human RecQ helicases participate in DNA repair, and more specifically in certain subpathways of DNA repair. Three of the RecQ helicases are deficient in disorders of premature aging: Werner syndrome, Bloom syndrome and Rothmund Thomson syndrome. Much less is known about the Rothmund-Thomson syndrome protein, RECQ4, and RecQ5 than about the other human RecQ helicases. We find that the RecQ4 protein participates in DNA repair of double and single strand breaks and that cells from individuals with this condition are defective in DNA repair. Biochemically, we are characterizing the RECQ4 protein and while its helicase function in many ways is similar to those of the WRN and BLM helicases, there are also significant differences. Moreover, we are currently exploring potential the protein interactions and protein complexes that RECQ4 participates in. RecQ5 is another member of the RecQ family for which little information is known. We have previously reported that WRN, BLM and RecQ4 can stimulate core base excision repair proteins. Thus we are evaluating whether RecQ5 can also stimulate and interact with BER proteins.