Journal article
Functions of human replication protein A (RPA): from DNA replication to DNA damage and stress responses
Journal of cellular physiology, Vol.208(2), pp.267-273
08/2006
Handle:
https://hdl.handle.net/2376/108563
PMCID: PMC3107514
PMID: 16523492
Abstract
Human replication protein A (RPA), a heterotrimeric protein complex, was originally defined as a eukaryotic single-stranded DNA binding (SSB) protein essential for the in vitro replication of simian virus 40 (SV40) DNA. Since then RPA has been found to be an indispensable player in almost all DNA metabolic pathways such as, but not limited to, DNA replication, DNA repair, recombination, cell cycle, and DNA damage checkpoints. Defects in these cellular reactions may lead to genome instability and, thus, the diseases with a high potential to evolve into cancer. This extensive involvement of RPA in various cellular activities implies a potential modulatory role for RPA in cellular responses to genotoxic insults. In support, RPA is hyperphosphorylated upon DNA damage or replication stress by checkpoint kinases including ataxia telangiectasia mutated (ATM), ATR (ATM and Rad3-related), and DNA-dependent protein kinase (DNA-PK). The hyperphosphorylation may change the functions of RPA and, thus, the activities of individual pathways in which it is involved. Indeed, there is growing evidence that hyperphosphorylation alters RPA-DNA and RPA-protein interactions. In addition, recent advances in understanding the molecular basis of the stress-induced modulation of RPA functions demonstrate that RPA undergoes a subtle structural change upon hyperphosphorylation, revealing a structure-based modulatory mechanism. Furthermore, given the crucial roles of RPA in a broad range of cellular processes, targeting RPA to inhibit its specific functions, particularly in DNA replication and repair, may serve a valuable strategy for drug development towards better cancer treatment.
Metrics
22 Record Views
Details
- Title
- Functions of human replication protein A (RPA): from DNA replication to DNA damage and stress responses
- Creators
- Yue Zou - Department of Biochemistry and Molecular Biology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614, USA. zouy@etsu.eduYiyong LiuXiaoming WuSteven M Shell
- Publication Details
- Journal of cellular physiology, Vol.208(2), pp.267-273
- Academic Unit
- Biomedical Sciences, Department of; Molecular Biosciences, School of
- Publisher
- United States
- Grant note
- R01 CA086927 / NCI NIH HHS R01 CA086927-05 / NCI NIH HHS R01 CA086927-04 / NCI NIH HHS R56 CA086927 / NCI NIH HHS CA86927 / NCI NIH HHS R01 CA086927-01 / NCI NIH HHS R01 CA086927-03 / NCI NIH HHS R01 CA086927-02 / NCI NIH HHS
- Identifiers
- 99900546990401842
- Language
- English
- Resource Type
- Journal article