Stability versus exchange: a paradox in DNA replication

被引:29
作者
Aberg, Christoffer [1 ]
Duderstadt, Karl E. [2 ]
van Oijen, Antoine M. [2 ,3 ]
机构
[1] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, NL-9747 AG Groningen, Netherlands
[2] Univ Groningen, Zernike Inst Adv Mat, NL-9747 AG Groningen, Netherlands
[3] Univ Wollongong, Sch Chem, Wollongong, NSW 2522, Australia
基金
欧洲研究理事会;
关键词
ESCHERICHIA-COLI; BACTERIOPHAGE T7; SINGLE-MOLECULE; POLYMERASE EXCHANGE; PROTEIN COMPLEXES; LEADING-STRAND; FORK; STOICHIOMETRY; REPLISOME; HELICASE;
D O I
10.1093/nar/gkw296
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Multi-component biological machines, comprising individual proteins with specialized functions, perform a variety of essential processes in cells. Once assembled, most such complexes are considered very stable, retaining individual constituents as long as required. However, rapid and frequent exchange of individual factors in a range of critical cellular assemblies, including DNA replication machineries, DNA transcription regulators and flagellar motors, has recently been observed. The high stability of a multiprotein complex may appear mutually exclusive with rapid subunit exchange. Here, we describe a multisite competitive exchange mechanism, based on simultaneous binding of a protein to multiple low-affinity sites. It explains how a component can be stably integrated into a complex in the absence of competing factors, while able to rapidly exchange in the presence of competing proteins. We provide a mathematical model for the mechanism and give analytical expressions for the stability of a pre-formed complex, in the absence and presence of competitors. Using typical binding kinetic parameters, we show that the mechanism is operational under physically realistic conditions. Thus, high stability and rapid exchange within a complex can be reconciled and this framework can be used to rationalize previous observations, qualitatively as well as quantitatively.
引用
收藏
页码:4846 / 4854
页数:9
相关论文
共 32 条
[1]   STUDIES ON DNA-REPLICATION IN THE BACTERIOPHAGE-T4 INVITRO SYSTEM [J].
ALBERTS, BM ;
BARRY, J ;
BEDINGER, P ;
FORMOSA, T ;
JONGENEEL, CV ;
KREUZER, KN .
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 1982, 47 :655-668
[2]  
[Anonymous], 1997, HDB STOCHASTIC METHO
[3]   Concentration- and chromosome-organization-dependent regulator unbinding from DNA for transcription regulation in living cells [J].
Chen, Tai-Yen ;
Santiago, Ace George ;
Jung, Won ;
Krzeminski, Lukasz ;
Yang, Feng ;
Martell, Danya J. ;
Helmann, John D. ;
Chen, Peng .
NATURE COMMUNICATIONS, 2015, 6
[4]   Stochastic Ratchet Mechanisms for Replacement of Proteins Bound to DNA [J].
Cocco, S. ;
Marko, J. F. ;
Monasson, R. .
PHYSICAL REVIEW LETTERS, 2014, 112 (23)
[5]   COORDINATION OF LEADING AND LAGGING-STRAND DNA-SYNTHESIS AT THE REPLICATION FORK OF BACTERIOPHAGE-T7 [J].
DEBYSER, Z ;
TABOR, S ;
RICHARDSON, CC .
CELL, 1994, 77 (01) :157-166
[6]   Single-molecule studies of polymerase dynamics and stoichiometry at the bacteriophage T7 replication machinery [J].
Geertsema, Hylkje J. ;
Kulczyk, Arkadiusz W. ;
Richardson, Charles C. ;
van Oijen, Antoine M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (11) :4073-4078
[7]   A single-molecule view of DNA replication: the dynamic nature of multi-protein complexes revealed [J].
Geertsema, Hylkje J. ;
van Oijen, Antoine M. .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 2013, 23 (05) :788-793
[8]   Concentration-Dependent Exchange of Replication Protein A on Single-Stranded DNA Revealed by Single-Molecule Imaging [J].
Gibb, Bryan ;
Ye, Ling F. ;
Gergoudis, Stephanie C. ;
Kwon, YoungHo ;
Niu, Hengyao ;
Sung, Patrick ;
Greene, Eric C. .
PLOS ONE, 2014, 9 (02)
[9]   Concentration-dependent exchange accelerates turnover of proteins bound to double-stranded DNA [J].
Graham, John S. ;
Johnson, Reid C. ;
Marko, John F. .
NUCLEIC ACIDS RESEARCH, 2011, 39 (06) :2249-2259
[10]   Dynamic DNA helicase-DNA polymerase interactions assure processive replication fork movement [J].
Hamdan, Samir M. ;
Johnson, Donald E. ;
Tanner, Nathan A. ;
Lee, Jong-Bong ;
Qimron, Udi ;
Tabor, Stanley ;
van Oijen, Antoine M. ;
Richardson, Charles C. .
MOLECULAR CELL, 2007, 27 (04) :539-549