Lesion bypass DNA polymerases replicate across non-DNA segments

被引:13
作者
Maor-Shoshani, A [1 ]
Ben-Ari, V [1 ]
Livneh, Z [1 ]
机构
[1] Weizmann Inst Sci, Dept Biochem Sci, IL-76100 Rehovot, Israel
关键词
D O I
10.1073/pnas.2433503100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A critical feature of the robustness of the DNA replication machinery is the ability to complete its task in the presence of interfering DNA damage. A key mechanism responsible for this task is translesion replication (also termed translesion synthesis), carried out by specialized lesion bypass DNA polymerases of the Y superfamily. Here we show that in Escherichia coli, plasmids can be replicated across a segment of foreign non-DNA material, consisting of hydrocarbon chains of 3 or 12 methylene residues. This replication is carried out by DNA polymerase V and proceeds by at least two mechanisms: (i) Editing out the foreign insert, by polymerase "hopping" across it, which can be mediated by looping out of the insert, leading to its deletion, while preserving the DNA sequence. (ii) DNA synthesis through the insert, which occurs by incorporating one or two nucleotides opposite the hydrocarbon chain, yielding a net increase in the length of the DNA sequence. The remarkable ability of DNA polymerase V to insert nucleotides opposite a hydrocarbon chain shows that DNA synthesis can occur in a region of the template strand, which lacks all fundamental features of DNA, including its purine, pyrimidine, sugar, and phosphate moieties, and its hydrophilic and ionic nature. This bypass ability reflects a striking robustness of the translesion replication apparatus and is likely to contribute to its effectiveness in maintaining genome stability.
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页码:14760 / 14765
页数:6
相关论文
共 41 条
[1]   Genetic variation: molecular mechanisms and impact on microbial evolution [J].
Arber, W .
FEMS MICROBIOLOGY REVIEWS, 2000, 24 (01) :1-7
[2]   Quantitative measurement of translesion replication in human cells: Evidence for bypass of abasic sites by a replicative DNA polymerase [J].
Avkin, S ;
Adar, S ;
Blander, G ;
Livneh, Z .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (06) :3764-3769
[3]   DNA lesion bypass polymerases open up [J].
Beard, WA ;
Wilson, SH .
STRUCTURE, 2001, 9 (09) :759-764
[4]   Error-free recombinational repair predominates over mutagenic translesion replication in E-coli [J].
Berdichevsky, A ;
Izhar, L ;
Livneh, Z .
MOLECULAR CELL, 2002, 10 (04) :917-924
[5]   Genome and protein evolution in eukaryotes [J].
Copley, RR ;
Letunic, I ;
Bork, P .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2002, 6 (01) :39-45
[6]   A broadening view of recombinational DNA repair in bacteria [J].
Cox, MM .
GENES TO CELLS, 1998, 3 (02) :65-78
[7]   FIDELITY MECHANISMS IN DNA-REPLICATION [J].
ECHOLS, H ;
GOODMAN, MF .
ANNUAL REVIEW OF BIOCHEMISTRY, 1991, 60 :477-511
[8]  
Efrati E, 1997, J BIOL CHEM, V272, P2559
[9]   Exchanging partners: Recombination in E-coli [J].
Eggleston, AK ;
West, SC .
TRENDS IN GENETICS, 1996, 12 (01) :20-26
[10]   Error-prone DNA polymerases: Novel structures and the benefits of infidelity [J].
Friedberg, EC ;
Fischhaber, PL ;
Kisker, C .
CELL, 2001, 107 (01) :9-12