Biochemical peculiarities of the different RPA homologues of Arabidopsis thaliana and their influence on enzymes involved in DNA repair and recombination
Biochemical peculiarities of the different RPA homologues of Arabidopsis thaliana and their influence on enzymes involved in DNA repair and recombination
批准号:
169487602
负责人:
Dr. Daniela Kobbe
金额:
$0.0万
依托单位国家:
德国
项目类别:
Research Grants
财政年份:
2010
资助国家:
德国
项目状态:
已结题
起止时间:
2009-12-31 至 2014-12-31
中文摘要
异源三聚体DNA单链结合蛋白RPA(复制蛋白A;典型地由RPA 1、RPA 2和RPA 3组成)参与DNA复制、修复和重组等基本过程。一种不同组成的变体(人类aRPA)可能会阻止特定组织中的DNA复制-这是癌症背景下的一个重要问题。有趣的是,模式植物拟南芥具有更复杂的RPA系统,因为它具有最大亚基RPA 1的五种不同同源物,以及RPA 2和RPA 3亚基的两种同源物。假设不同的复合物执行不同的功能(例如在修复、重组、复制中)。不同的旁系同源物执行特定功能的理论也在RECQ解旋酶家族中得到例证,其中单个同源物对于修复、重组和复制是重要的。典型的人RPA显示出在体外刺激不同解旋酶的解旋活性,也刺激人RECQ解旋酶的解旋活性。由此产生的问题,是否以及如何不同的拟南芥RPA复合物影响不同的拟南芥RECQ解旋酶的活动,应加以解决。这将有助于进一步剖析专门职能。该分析应扩展到其他DNA加工蛋白。对于人类范可尼贫血蛋白FANCJ有趣的功能相互作用与RPA被证明。因此,FANCJ的两个拟南芥同源物,这也是普遍感兴趣的,应制备和分析。
英文摘要
The heterotrimeric DNA single strand binding protein RPA (Replication protein A; canonically composed of RPA1, RPA2 and RPA3) is involved in essential processes like DNA replication, repair and recombination. A differently composed variant (human aRPA) presumably prevents DNA replication in defined tissues - an important issue in the context of cancer. Interestingly, the model plant Arabidopsis thaliana features an even more complex RPA system, as it possesses five different homologs of the largest subunit RPA1, and two homologs of both the RPA2 and the RPA3 subunits. It is assumed that different complexes perform different functions (e.g. in repair, recombination, replication). The theory, that different paralogs perform specialized functions is also exemplified in the RECQ helicase family, with individual homologs being important for repair, recombination and replication. Canonical human RPA was shown to stimulate the unwinding activity of different helicases in vitro, also of the human RECQ helicases. The resulting question of whether and how the different Arabidopsis RPA complexes affect the activities of the different Arabidopsis RECQ helicases should be addressed. This should help to further dissect specialized functions. The analysis should be extended to other DNA processing proteins. For the human Fanconi anemia protein FANCJ interesting functional interactions with RPA were demonstrated. Therefore, the two Arabidopsis homologs of FANCJ, which are also of general interest, should be prepared and analyzed.
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