Year-end Sale % OFF 
Abstract
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.
Highlights
Helicases are molecular motors that use the energy of nucleoside triphosphate binding and hydrolysis to fuel the separation of the many hydrogen bonds between complementary nucleic acid sequences [1,2,3]
The functions of DNA helicases and specialized molecular motors known as translocases that move along single-stranded or double-stranded DNA are important for DNA repair and maintenance of genomic stability [8,9,10,11]; an expanding number of genetic disorders are linked to mutations in helicase/translocase genes [12,13,14,15,16,17,18,19,20]
Biochemical and cellular studies have provided strong evidence that eukaryotic DNA helicases coordinate their activities with Replication Protein A (RPA) in the context of DNA repair, replication stress response, fork remodeling, checkpoint activation, and telomere metabolism
Summary
Helicases are molecular motors that use the energy of nucleoside triphosphate binding and hydrolysis to fuel the separation of the many hydrogen bonds between complementary nucleic acid sequences [1,2,3]. Biochemical, genetic, and cellular studies have clearly demonstrated that RPA plays significant roles in replication and the checkpoint response [27], recombination [28,29,30], and DNA repair mediated in part by its protein interactions [31,32]. The requirement of RPA for cell viability may help to explain why to date there are no genetic diseases linked to RPA mutations because the single-stranded DNA binding protein is essential for life. It remains to be seen if any RPA hypomorphic mutations associated with a reduction in gene expression or partial loss of function are implicated in a disease condition. The collective studies in the field provide strong evidence that helicases/translocases and RPA perform DNA transactions in a concerted manner to maintain cellular and genomic integrity
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
