Premium
Functions of human replication protein A (RPA): From DNA replication to DNA damage and stress responses
Author(s) -
Zou Yue,
Liu Yiyong,
Wu Xiaoming,
Shell Steven M.
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20622
Subject(s) - replication protein a , dna replication , dna damage , eukaryotic dna replication , dna repair , hyperphosphorylation , biology , microbiology and biotechnology , replication factor c , dna replication factor cdt1 , control of chromosome duplication , dna re replication , dna , origin recognition complex , kinase , dna binding protein , genetics , gene , transcription factor
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. J. Cell. Physiol. 208: 267–273, 2006. © 2006 Wiley‐Liss, Inc.