Faculty Publications
Document Type
Article
Publication Version
Published Version
Keywords
Genome integrity, repair and replication
Journal/Book/Conference Title
Nucleic Acids Research
Volume
52
Issue
20
First Page
12422
Last Page
12437
Abstract
Human replication protein A (RPA) is a heterotrimeric ssDNA binding protein responsible for many aspects of cellular DNA metabolism. Dynamic interactions of the four RPA DNA binding domains (DBDs) with DNA control replacement of RPA by downstream proteins in various cellular metabolic pathways. RPA plays several important functions at telomeres where it binds to and melts telomeric G-quadruplexes, non-canonical DNA structures formed at the G-rich telomeric ssDNA overhangs. Here, we combine single-molecule total internal reflection fluorescence microscopy (smTIRFM) and mass photometry (MP) with biophysical and biochemical analyses to demonstrate that heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) specifically remodels RPA bound to telomeric ssDNA by dampening the RPA configurational dynamics and forming a ternary complex. Uniquely, among hnRNPA1 target RNAs, telomeric repeat-containing RNA (TERRA) is selectively capable of releasing hnRNPA1 from the RPA-telomeric DNA complex. We speculate that this telomere specific RPA-DNA-hnRNPA1 complex is an important structure in telomere protection.
Department
Department of Physics
Original Publication Date
11-11-2024
Object Description
1 PDF File
DOI of published version
10.1093/nar/gkae834
Repository
UNI ScholarWorks, Rod Library, University of Northern Iowa
Copyright
©2024 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Language
en
File Format
application/pdf
Recommended Citation
Granger, Sophie L.; Sharma, Richa; Kaushik, Vikas; Razzaghi, Mortezaali; Honda, Masayoshi; Gaur, Paras; Bhat, Divya S.; Labenz, Sabryn M.; Heinen, Jenna E.; Williams, Blaine A.; Tabei, S. M. Ali; and Wlodarski, Marcin W., "Human hnRNPA1 Reorganizes Telomere-Bound Replication Protein A" (2024). Faculty Publications. 6696.
https://scholarworks.uni.edu/facpub/6696
Comments
First published in Nucleic Acids Research, v52 (2024) published by Oxford University Press. DOI: https://doi.org/10.1093/nar/gkae834