Interactive Roles of DNA Helicases and Translocases with the Single-Stranded DNA Binding Protein RPA in Nucleic Acid Metabolism.

Interactive Roles of DNA Helicases and Translocases with the Single-Stranded DNA Binding Protein RPA in Nucleic Acid Metabolism.
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DOI:
10.3390/ijms18061233
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发表时间:
2017-06-08
影响因子:
5.6
通讯作者:
Brosh RM Jr
Brosh RM Jr
中科院分区:
生物学2区
文献类型:
--
作者:
Awate S;Brosh RM Jr

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解旋酶和转座酶分别利用核苷三磷酸结合和水解的能量来解开/分解结构核酸或沿着单链或双链多核苷酸链移动。这些分子马达促进各种交易,包括复制,DNA修复,重组和转录。真核生物DNA解旋酶/转位酶的关键伙伴是单链DNA结合蛋白复制蛋白A (RPA)。生化、遗传和细胞生物学分析表明,RPA在物理和功能上与这些人类分子马达相互作用,并且它们的关联在经历复制应激的细胞中丰富。DNA解旋酶/转位酶在核酸代谢途径中的作用与RPA协调一致。RPA刺激解旋酶催化的DNA解绕,使转位酶进入作用位点,并调节其在DNA修复、叉重构、检查点激活和端粒维持中的活性。DNA解旋酶/转位酶和RPA之间的动态相互作用才刚刚开始在分子和细胞水平上被理解,还有很多东西需要学习,这可能会为潜在的治疗策略提供信息。
Helicases and translocases use the energy of nucleoside triphosphate binding and hydrolysis to unwind/resolve structured nucleic acids or move along a single-stranded or double-stranded polynucleotide chain, respectively. These molecular motors facilitate a variety of transactions including replication, DNA repair, recombination, and transcription. A key partner of eukaryotic DNA helicases/translocases is the single-stranded DNA binding protein Replication Protein A (RPA). Biochemical, genetic, and cell biological assays have demonstrated that RPA interacts with these human molecular motors physically and functionally, and their association is enriched in cells undergoing replication stress. The roles of DNA helicases/translocases are orchestrated with RPA in pathways of nucleic acid metabolism. RPA stimulates helicase-catalyzed DNA unwinding, enlists translocases to sites of action, and modulates their activities in DNA repair, fork remodeling, checkpoint activation, and telomere maintenance. The dynamic interplay between DNA helicases/translocases and RPA is just beginning to be understood at the molecular and cellular levels, and there is still much to be learned, which may inform potential therapeutic strategies.