PMID:18158902: Difference between revisions

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<span style = 'font-size: large'> '''Godoy, VG, Jarosz, DF, Simon, SM, Abyzov, A, Ilyin, V and Walker, GC'''  (2007) UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinB.''Mol. Cell'' '''28''':1058-70</span>
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|{{TableHeadingColor}} |'''Abstract''' || <protect>DinB is the only translesion Y family DNA polymerase conserved among bacteria, archaea, and eukaryotes. DinB and its orthologs possess a specialized lesion bypass function but also display potentially deleterious -1 frameshift mutagenic phenotypes when overproduced. We show that the DNA damage-inducible proteins UmuD(2) and RecA act in concert to modulate this mutagenic activity. Structural modeling suggests that the relatively open active site of DinB is enclosed by interaction with these proteins, thereby preventing the template bulging responsible for -1 frameshift mutagenesis. Intriguingly, residues that define the UmuD(2)-interacting surface on DinB statistically covary throughout evolution, suggesting a driving force for the maintenance of a regulatory protein-protein interaction at this site. Together, these observations indicate that proteins like RecA and UmuD(2) may be responsible for managing the mutagenic potential of DinB orthologs throughout evolution.</protect>
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'''Godoy, VG, Jarosz, DF, Simon, SM, Abyzov, A, Ilyin, V and Walker, GC''' (2007) UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinB. ''Mol. Cell'' '''28''':1058-70
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DinB is the only translesion Y family DNA polymerase conserved among bacteria, archaea, and eukaryotes. DinB and its orthologs possess a specialized lesion bypass function but also display potentially deleterious -1 frameshift mutagenic phenotypes when overproduced. We show that the DNA damage-inducible proteins UmuD(2) and RecA act in concert to modulate this mutagenic activity. Structural modeling suggests that the relatively open active site of DinB is enclosed by interaction with these proteins, thereby preventing the template bulging responsible for -1 frameshift mutagenesis. Intriguingly, residues that define the UmuD(2)-interacting surface on DinB statistically covary throughout evolution, suggesting a driving force for the maintenance of a regulatory protein-protein interaction at this site. Together, these observations indicate that proteins like RecA and UmuD(2) may be responsible for managing the mutagenic potential of DinB orthologs throughout evolution.
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[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18158902 PubMed] [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265384 PMC2265384]
Online version:[http://dx.doi.org/10.1016/j.molcel.2007.10.025 10.1016/j.molcel.2007.10.025]
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|{{TableHeadingColor}} nowrap |'''Links''' ||  [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18158902 PubMed]<br/>Online version:[http://dx.doi.org/10.1016/j.molcel.2007.10.025 10.1016/j.molcel.2007.10.025]
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Amino Acid Sequence; Binding Sites/genetics; Blotting, Far-Western; DNA Polymerase beta/chemistry; DNA Polymerase beta/genetics; DNA Polymerase beta/metabolism; DNA-Directed DNA Polymerase/chemistry; DNA-Directed DNA Polymerase/genetics; DNA-Directed DNA Polymerase/metabolism; Escherichia coli/enzymology; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Models, Molecular; Molecular Sequence Data; Mutagenesis; Mutation; Protein Binding; Protein Structure, Tertiary; Rec A Recombinases/chemistry; Rec A Recombinases/genetics; Rec A Recombinases/metabolism; Sequence Homology, Amino Acid
 
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Latest revision as of 04:33, 15 September 2013

Citation

Godoy, VG, Jarosz, DF, Simon, SM, Abyzov, A, Ilyin, V and Walker, GC (2007) UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinB. Mol. Cell 28:1058-70

Abstract

DinB is the only translesion Y family DNA polymerase conserved among bacteria, archaea, and eukaryotes. DinB and its orthologs possess a specialized lesion bypass function but also display potentially deleterious -1 frameshift mutagenic phenotypes when overproduced. We show that the DNA damage-inducible proteins UmuD(2) and RecA act in concert to modulate this mutagenic activity. Structural modeling suggests that the relatively open active site of DinB is enclosed by interaction with these proteins, thereby preventing the template bulging responsible for -1 frameshift mutagenesis. Intriguingly, residues that define the UmuD(2)-interacting surface on DinB statistically covary throughout evolution, suggesting a driving force for the maintenance of a regulatory protein-protein interaction at this site. Together, these observations indicate that proteins like RecA and UmuD(2) may be responsible for managing the mutagenic potential of DinB orthologs throughout evolution.

Links

PubMed PMC2265384 Online version:10.1016/j.molcel.2007.10.025

Keywords

Amino Acid Sequence; Binding Sites/genetics; Blotting, Far-Western; DNA Polymerase beta/chemistry; DNA Polymerase beta/genetics; DNA Polymerase beta/metabolism; DNA-Directed DNA Polymerase/chemistry; DNA-Directed DNA Polymerase/genetics; DNA-Directed DNA Polymerase/metabolism; Escherichia coli/enzymology; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Models, Molecular; Molecular Sequence Data; Mutagenesis; Mutation; Protein Binding; Protein Structure, Tertiary; Rec A Recombinases/chemistry; Rec A Recombinases/genetics; Rec A Recombinases/metabolism; Sequence Homology, Amino Acid

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