Biochemical peculiarities of the different RPA homologues of Arabidopsis thaliana and their influence on enzymes involved in DNA repair and recombination

拟南芥不同 RPA 同源物的生化特性及其对 DNA 修复和重组酶的影响

• 批准号: 169487602
• 负责人: Dr. Daniela Kobbe
• 金额: --
• 依托单位: Arbeitsgruppe Molekularbiologie und Biochemie
• 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
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/169487602?language=en
• 关键词: Biochemical; peculiarities; different; RPA; homologues

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.

异三聚体DNA单链结合蛋白RPA(复制蛋白A，通常由RPA1、RPA2和RPA3组成)参与DNA复制、修复和重组等重要过程。一种结构不同的变异体(人类ARPA)可能会阻止DNA在特定组织中复制--这在癌症的背景下是一个重要的问题。有趣的是，模式植物拟南芥具有一个更复杂的RPA系统，因为它拥有最大亚基RPA1的五个不同同源物，以及RPA2和RPA3亚基的两个同源物。假设不同的复合体执行不同的功能(例如，在修复、重组、复制中)。不同的类似物执行特殊功能的理论也在RecQ解旋酶家族中得到例证，单个同源物对于修复、重组和复制是重要的。规范的人RPA在体外可以刺激不同解旋酶的解离活性，也可以刺激人RecQ解旋酶的解离活性。由此产生的问题是，不同的拟南芥RPA复合体是否以及如何影响不同的拟南芥RecQ解旋酶的活性。这应该有助于进一步剖析专门的职能。这种分析应该扩展到其他DNA加工蛋白。对于人类Fanconi贫血蛋白，FANCJ与RPA发生了有趣的功能相互作用。因此，FANCJ的两个拟南芥同源基因也是人们普遍感兴趣的，应该进行制备和分析。