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Stanley N Cohen - One of the best experts on this subject based on the ideXlab platform.
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ribonuclease e modulation of the bacterial SOS Response
PLOS ONE, 2012Co-Authors: Robert Manasherob, Christine A Miller, Stanley N CohenAbstract:Plants, animals, bacteria, and Archaea all have evolved mechanisms to cope with environmental or cellular stress. Bacterial cells respond to the stress of DNA damage by activation of the SOS Response, the canonical RecA/LexA-dependent signal transduction pathway that transcriptionally derepresses a multiplicity of genes–leading to transient arrest of cell division and initiation of DNA repair. Here we report the previously unsuspected role of E. coli endoribonuclease RNase E in regulation of the SOS Response. We show that RNase E deletion or inactivation of temperature-sensitive RNase E protein precludes normal initiation of SOS. The ability of RNase E to regulate SOS is dynamic, as down regulation of RNase E following DNA damage by mitomycin C resulted in SOS termination and restoration of RNase E function leads to resumption of a previously aborted Response. Overexpression of the RraA protein, which binds to the C-terminal region of RNase E and modulates the actions of degradosomes, recapitulated the effects of RNase E deficiency. Possible mechanisms for RNase E effects on SOS are discussed.
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SOS Response induction by β lactams and bacterial defense against antibiotic lethality
Science, 2004Co-Authors: Christine A Miller, Line Elnif Thomsen, Carina Gaggero, Ronen Mosseri, Hanne Ingmer, Stanley N CohenAbstract:The SOS Response aids bacterial propagation by inhibiting cell division during repair of DNA damage. We report that inactivation of the ftsI gene product, penicillin binding protein 3, by either β-lactam antibiotics or genetic mutation induces SOS in Escherichia coli through the DpiBA two-component signal transduction system. This event, which requires the SOS-promoting recA and lexA genes as well as dpiA , transiently halts bacterial cell division, enabling survival to otherwise lethal antibiotic exposure. Our findings reveal defective cell wall synthesis as an unexpected initiator of the bacterial SOS Response, indicate that β-lactam antibiotics are extracellular stimuli of this Response, and demonstrate a novel mechanism for mitigation of antimicrobial lethality.
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SOS Response induction by s lactams and bacterial defense against antibiotic lethality
Science, 2004Co-Authors: Christine A Miller, Line Elnif Thomsen, Carina Gaggero, Ronen Mosseri, Hanne Ingmer, Stanley N CohenAbstract:The SOS Response aids bacterial propagation by inhibiting cell division during repair of DNA damage. We report that inactivation of the ftsI gene product, penicillin binding protein 3, by either β-lactam antibiotics or genetic mutation induces SOS in Escherichia coli through the DpiBA two-component signal transduction system. This event, which requires the SOS-promoting recA and lexA genes as well as dpiA , transiently halts bacterial cell division, enabling survival to otherwise lethal antibiotic exposure. Our findings reveal defective cell wall synthesis as an unexpected initiator of the bacterial SOS Response, indicate that β-lactam antibiotics are extracellular stimuli of this Response, and demonstrate a novel mechanism for mitigation of antimicrobial lethality.
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dpia binding to the replication origin of escherichia coli plasmids and chromosomes destabilizes plasmid inheritance and induces the bacterial SOS Response
Journal of Bacteriology, 2003Co-Authors: Christine A Miller, Line Elnif Thomsen, Hanne Ingmer, Kirsten Skarstad, Stanley N CohenAbstract:The dpiA and dpiB genes of Escherichia coli, which are orthologs of genes that regulate citrate uptake and utilization in Klebsiella pneumoniae, comprise a two-component signal transduction system that can modulate the replication of and destabilize the inheritance of pSC101 and certain other plasmids. Here we show that perturbed replication and inheritance result from binding of the effector protein DpiA to A+T-rich replication origin sequences that resemble those in the K. pneumoniae promoter region targeted by the DpiA ortholog, CitB. Consistent with its ability to bind to A+T-rich origin sequences, overproduction of DpiA induced the SOS Response in E. coli, suggesting that chromosomal DNA replication is affected. Bacteria that overexpressed DpiA showed an increased amount of DNA per cell and increased cell size-both also characteristic of the SOS Response. Concurrent overexpression of the DNA replication initiation protein, DnaA, or the DNA helicase, DnaB-both of which act at A+T-rich replication origin sequences in the E. coli chromosome and DpiA-targeted plasmids-reversed SOS induction as well as plasmid destabilization by DpiA. Our finding that physical and functional interactions between DpiA and sites of replication initiation modulate DNA replication and plasmid inheritance suggests a mechanism by which environmental stimuli transmitted by these gene products can regulate chromosomal and plasmid dynamics.
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the repa protein of plasmid psc101 controls escherichia coli cell division through the SOS Response
Molecular Microbiology, 2001Co-Authors: Hanne Ingmer, Christine L Miller, Stanley N CohenAbstract:Although plasmid copy number varies widely among different plasmid species, normally copy number is maintained within a narrow range for any given plasmid. Such copy number control has been shown to occur by regulation of the rate of plasmid DNA replication. Here we report a novel mechanism by which the pSC101 plasmid also can detect an imbalance between the cellular level of its replication protein, RepA, and plasmid-borne RepA binding sites to inhibit bacterial DNA replication and delay host cell division when RepA is in relative excess. We show that delayed cell division occurs by RepA-mediated induction of the SOS Response and can be reversed by over-expression of the host DNA primase, DnaG. The effects of RepA excess are prevented by introducing a surfeit of RepA binding sites. The mechanism reported here may help to limit variation in plasmid copy number and allow repopulation of cells with plasmids when copy number falls--potentially pre-empting plasmid loss in cultures of dividing cells.
Lakshminarayan M Iyer - One of the best experts on this subject based on the ideXlab platform.
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novel autoproteolytic and dna damage sensing components in the bacterial SOS Response and oxidized methylcytosine induced eukaryotic dna demethylation systems
Biology Direct, 2013Co-Authors: L Aravind, Swadha Anand, Lakshminarayan M IyerAbstract:The bacterial SOS Response is an elaborate program for DNA repair, cell cycle regulation and adaptive mutagenesis under stress conditions. Using sensitive sequence and structure analysis, combined with contextual information derived from comparative genomics and domain architectures, we identify two novel domain superfamilies in the SOS Response system. We present evidence that one of these, the SOS Response associated peptidase (SRAP; Pfam: DUF159) is a novel thiol autopeptidase. Given the involvement of other autopeptidases, such as LexA and UmuD, in the SOS Response, this finding suggests that multiple structurally unrelated peptidases have been recruited to this process. The second of these, the ImuB-C superfamily, is linked to the Y-family DNA polymerase-related domain in ImuB, and also occurs as a standalone protein. We present evidence using gene neighborhood analysis that both these domains function with different mutagenic polymerases in bacteria, such as Pol IV (DinB), Pol V (UmuCD) and ImuA-ImuB-DnaE2 and also other repair systems, which either deploy Ku and an ATP-dependent ligase or a SplB-like radical SAM photolyase. We suggest that the SRAP superfamily domain functions as a DNA-associated autoproteolytic switch that recruits diverse repair enzymes upon DNA damage, whereas the ImuB-C domain performs a similar function albeit in a non-catalytic fashion. We propose that C3Orf37, the eukaryotic member of the SRAP superfamily, which h as been recently shown to specifically bind DNA with 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine, is a sensor for these oxidized bases generated by the TET enzymes from methylcytosine. Hence, its autoproteolytic activity might help it act as a switch that recruits DNA repair enzymes to remove these oxidized methylcytosine species as part of the DNA demethylation pathway downstream of the TET enzymes. Reviewers: This article was reviewed by RDS, RF and GJ.
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novel autoproteolytic and dna damage sensing components in the bacterial SOS Response and oxidized methylcytosine induced eukaryotic dna demethylation systems
Biology Direct, 2013Co-Authors: L Aravind, Swadha Anand, Lakshminarayan M IyerAbstract:The bacterial SOS Response is an elaborate program for DNA repair, cell cycle regulation and adaptive mutagenesis under stress conditions. Using sensitive sequence and structure analysis, combined with contextual information derived from comparative genomics and domain architectures, we identify two novel domain superfamilies in the SOS Response system. We present evidence that one of these, the SOS Response associated peptidase (SRAP; Pfam: DUF159) is a novel thiol autopeptidase. Given the involvement of other autopeptidases, such as LexA and UmuD, in the SOS Response, this finding suggests that multiple structurally unrelated peptidases have been recruited to this process. The second of these, the ImuB-C superfamily, is linked to the Y-family DNA polymerase-related domain in ImuB, and also occurs as a standalone protein. We present evidence using gene neighborhood analysis that both these domains function with different mutagenic polymerases in bacteria, such as Pol IV (DinB), Pol V (UmuCD) and ImuA-ImuB-DnaE2 and also other repair systems, which either deploy Ku and an ATP-dependent ligase or a SplB-like radical SAM photolyase. We suggest that the SRAP superfamily domain functions as a DNA-associated autoproteolytic switch that recruits diverse repair enzymes upon DNA damage, whereas the ImuB-C domain performs a similar function albeit in a non-catalytic fashion. We propose that C3Orf37, the eukaryotic member of the SRAP superfamily, which has been recently shown to specifically bind DNA with 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine, is a sensor for these oxidized bases generated by the TET enzymes from methylcytosine. Hence, its autoproteolytic activity might help it act as a switch that recruits DNA repair enzymes to remove these oxidized methylcytosine species as part of the DNA demethylation pathway downstream of the TET enzymes. This article was reviewed by RDS, RF and GJ.
Graham C Walker - One of the best experts on this subject based on the ideXlab platform.
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biological cost of pyocin production during the SOS Response in pseudomonas aeruginosa
Journal of Bacteriology, 2014Co-Authors: Jon Penterman, Pradeep K Singh, Graham C WalkerAbstract:LexA and two structurally related regulators, PrtR and PA0906, coordinate the Pseudomonas aeruginosa SOS Response. RecA-mediated autocleavage of LexA induces the expression of a protective set of genes that increase DNA damage repair and tolerance. In contrast, RecA-mediated autocleavage of PrtR induces antimicrobial pyocin production and a program that lyses cells to release the newly synthesized pyocin. Recently, PrtR-regulated genes were shown to sensitize P. aeruginosa to quinolones, antibiotics that elicit a strong SOS Response. Here, we investigated the mechanisms by which PrtR-regulated genes determine antimicrobial resistance and genotoxic stress survival. We found that induction of PrtR-regulated genes lowers resistance to clinically important antibiotics and impairs the survival of bacteria exposed to one of several genotoxic agents. Two distinct mechanisms mediated these effects. Cell lysis genes that are induced following PrtR autocleavage reduced resistance to bactericidal levels of ciprofloxacin, and production of extracellular R2 pyocin was lethal to cells that initially survived UV light treatment. Although typically resistant to R2 pyocin, P. aeruginosa becomes transiently sensitive to R2 pyocin following UV light treatment, likely because of the strong downregulation of lipopolysaccharide synthesis genes that are required for resistance to R2 pyocin. Our results demonstrate that pyocin production during the P. aeruginosa SOS Response carries both expected and unexpected costs.
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signal transduction in the escherichia coli SOS Response
Handbook of Cell Signaling (Second Edition), 2010Co-Authors: James J Foti, Lyle A Simmons, Penny J Beuning, Graham C WalkerAbstract:Publisher Summary This chapter provides a synoptic view on signal transduction in the Escherichia coli SOS Response. The gram-negative bacterium Escherichia coli activates a transcriptional circuit, known as the SOS Response following DNA damage or replicative stress. The SOS Response has two key antagonistic regulatory proteins, LexA (negative) and RecA, (positive) that control the expression of 57 genes. The RecA/ssDNA filament serves as the signal for the SOS Response, which is transduced through LexA resulting in the self-cleavage of LexA and de-repression of the 57 genes that are under LexA control. The intramolecular cleavage of the 22.7 kDa LexA repressor occurs between the Ala 84 -Gly 85 bonds resulting in nearly equally sized protein fragments. The LexA N-terminal fragment retains some DNA binding activity and can decrease gene expression. The newly generated N-terminus of LexA is recognized and targeted for degradation by the ClpXP ATP dependent protease, ensuring full SOS induction. In the E. coli RecA/ssDNA filament structure Lys 248 and Lys 250 coordinate a non-hydrolyzable ATP analog that mimics the transition state of ATP hydrolysis. These interactions are thought to stabilize the RecA-RecA interface and aid the transition to an active filament. Indeed, RecA K248A is deficient in ssDNA binding and ATP hydrolysis in vitro and DNA repair and recombination in vivo supporting the importance of Lys 248 in formation of the active filament. Several protein interactions modulate RecA filament assembly and stability thereby modulating the magnitude of SOS induction. These proteins include SSB, RecX, and DinI. DinI and RecX directly bind the RecA filament resulting in either filament stabilization or polymerization arrest.
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the SOS Response recent insights into umudc dependent mutagenesis and dna damage tolerance
Annual Review of Genetics, 2000Co-Authors: Mark D Sutton, Bradley T Smith, Veronica G Godoy, Graham C WalkerAbstract:Be they prokaryotic or eukaryotic, organisms are exposed to a multitude of deoxyribonucleic acid (DNA) damaging agents ranging from ultraviolet (UV) light to fungal metabolites, like Aflatoxin B1. Furthermore, DNA damaging agents, such as reactive oxygen species, can be produced by cells themselves as metabolic byproducts and intermediates. Together, these agents pose a constant threat to an organism's genome. As a result, organisms have evolved a number of vitally important mechanisms to repair DNA damage in a high fidelity manner. They have also evolved systems (cell cycle checkpoints) that delay the resumption of the cell cycle after DNA damage to allow more time for these accurate processes to occur. If a cell cannot repair DNA damage accurately, a mutagenic event may occur. Most bacteria, including Escherichia coli, have evolved a coordinated Response to these challenges to the integrity of their genomes. In E. coli, this inducible system is termed the SOS Response, and it controls both accurate and potentially mutagenic DNA repair functions [reviewed comprehensively in () and also in ()]. Recent advances have focused attention on the umuD(+)C(+)-dependent, translesion DNA synthesis (TLS) process that is responsible for SOS mutagenesis (). Here we discuss the SOS Response of E. coli and concentrate in particular on the roles of the umuD(+)C(+) gene products in promoting cell survival after DNA damage via TLS and a primitive DNA damage checkpoint.
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mutagenesis and more umudc and the escherichia coli SOS Response
Genetics, 1998Co-Authors: Bradley T Smith, Graham C WalkerAbstract:The cellular Response to DNA damage that has been most extensively studied is the SOS Response of Escherichia coli. Analyses of the SOS Response have led to new insights into the transcriptional and post-translational regulation of processes that increase cell survival after DNA damage as well as insights into DNA-damage-induced mutagenesis, i.e., SOS mutagenesis. SOS mutagenesis requires the recA and umuDC gene products and has as its mechanistic basis the alteration of DNA polymerase III such that it becomes capable of replicating DNA containing miscoding and noncoding lesions. Ongoing investigations of the mechanisms underlying SOS mutagenesis, as well as recent observations suggesting that the umuDC operon may have a role in the regulation of the E. coli cell cycle after DNA damage has occurred, are discussed.
Jordi Barbe - One of the best experts on this subject based on the ideXlab platform.
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non canonical lexa proteins regulate the SOS Response in the bacteroidetes
Nucleic Acids Research, 2021Co-Authors: Miquel Sanchezosuna, Jordi Barbe, Ivan Erill, Pilar Cortes, Mark Lee, Aaron T SmithAbstract:Lesions to DNA compromise chromosome integrity, posing a direct threat to cell survival. The bacterial SOS Response is a widespread transcriptional regulatory mechanism to address DNA damage. This Response is coordinated by the LexA transcriptional repressor, which controls genes involved in DNA repair, mutagenesis and cell-cycle control. To date, the SOS Response has been characterized in most major bacterial groups, with the notable exception of the Bacteroidetes. No LexA homologs had been identified in this large, diverse and ecologically important phylum, suggesting that it lacked an inducible mechanism to address DNA damage. Here, we report the identification of a novel family of transcriptional repressors in the Bacteroidetes that orchestrate a canonical Response to DNA damage in this phylum. These proteins belong to the S24 peptidase family, but are structurally different from LexA. Their N-terminal domain is most closely related to CI-type bacteriophage repressors, suggesting that they may have originated from phage lytic phase repressors. Given their role as SOS regulators, however, we propose to designate them as non-canonical LexA proteins. The identification of a new class of repressors orchestrating the SOS Response illuminates long-standing questions regarding the origin and plasticity of this transcriptional network.
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Molecular Interaction and Cellular Location of RecA and CheW Proteins in Salmonella enterica during SOS Response and Their Implication in Swarming
Frontiers in microbiology, 2016Co-Authors: Oihane Irazoki, Susana Campoy, Jesús Aranda, Timo Zimmermann, Jordi BarbeAbstract:In addition to its role in DNA damage repair and recombination, the RecA protein, through its interaction with CheW, is involved in swarming motility, a form of flagella-dependent movement across surfaces. In order to better understand how SOS Response modulates swarming, in this work the location of RecA and CheW proteins within the swarming cells has been studied by using super-resolution microscopy. Further, and after in silico docking studies, the specific RecA and CheW regions associated with the RecA-CheW interaction have also been confirmed by site-directed mutagenesis and immunoprecipitation techniques. Our results point out that the CheW distribution changes, from the cell poles to foci distributed in a helical pattern along the cell axis when SOS Response is activated or RecA protein is overexpressed. In this situation, the CheW presents the same subcellular location as that of RecA, pointing out that the previously described RecA storage structures may be modulators of swarming motility. Data reported herein not only confirmed that the RecA-CheW pair is essential for swarming motility but it is directly involved in the CheW distribution change associated to SOS Response activation. A model explaining not only the mechanism by which DNA damage modulates swarming but also how both the lack and the excess of RecA protein impair this motility is proposed.
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analysis of the SOS Response of vibrio and other bacteria with multiple chromosomes
BMC Genomics, 2012Co-Authors: Susana Campoy, Jordi Barbe, Neus Sanchezalberola, Ivan ErillAbstract:The SOS Response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS Response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. Our analysis provides the first comprehensive description of the SOS Response in a family (Vibrionaceae) that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS Response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS Response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. Our findings confirm that the SOS Response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS Response plays an essential role in these organisms and sheds light into the mechanisms of evolution of global transcriptional networks involved in adaptability and rapid Response to environmental changes, suggesting that small chromosomes may act as evolutionary test beds for the rewiring of transcriptional networks.
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The SOS Response controls integron recombination
Science, 2009Co-Authors: Emilie Guérin, Susana Campoy, Jordi Barbe, Ivan Erill, Mariececile Ploy, Guillaume Cambray, Neus Sanchez-alberola, Bruno Gonzalez-zorn, Didier MazelAbstract:Integrons are found in the genome of hundreds of environmental bacteria but are mainly known for their role in the capture and spread of antibiotic resistance determinants among Gram-negative pathogens. We report a direct link between this system and the ubiquitous SOS Response. We found that LexA controlled expression of most integron integrases and consequently regulated cassette recombination. This regulatory coupling enhanced the potential for cassette swapping and capture in cells under stress, while minimizing cassette rearrangements or loss in constant environments. This finding exposes integrons as integrated adaptive systems and has implications for antibiotic treatment policies.
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aeons of distress an evolutionary perspective on the bacterial SOS Response
Fems Microbiology Reviews, 2007Co-Authors: Ivan Erill, Susana Campoy, Jordi BarbeAbstract:The SOS Response of bacteria is a global regulatory network targeted at addressing DNA damage. Governed by the products of the lexA and recA genes, it co-ordinates a comprehensive Response against DNA lesions and its description in Escherichia coli has stood for years as a textbook paradigm of stress-Response systems in bacteria. In this paper we review the current state of research on the SOS Response outside E. coli. By retracing research on the identification of multiple diverging LexA-binding motifs across the Bacteria Domain, we show how this work has led to the description of a minimum regulon core, but also of a heterogeneous collection of SOS regulatory networks that challenges many tenets of the E. coli model. We also review recent attempts at reconstructing the evolutionary history of the SOS network that have cast new light on the SOS Response. Exploiting the newly gained knowledge on LexA-binding motifs and the tight association of LexA with a recently described mutagenesis cassette, these works put forward likely evolutionary scenarios for the SOS Response, and we discuss their relevance on the ultimate nature of this stress-Response system and the evolutionary pressures driving its evolution.
L Aravind - One of the best experts on this subject based on the ideXlab platform.
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novel autoproteolytic and dna damage sensing components in the bacterial SOS Response and oxidized methylcytosine induced eukaryotic dna demethylation systems
Biology Direct, 2013Co-Authors: L Aravind, Swadha Anand, Lakshminarayan M IyerAbstract:The bacterial SOS Response is an elaborate program for DNA repair, cell cycle regulation and adaptive mutagenesis under stress conditions. Using sensitive sequence and structure analysis, combined with contextual information derived from comparative genomics and domain architectures, we identify two novel domain superfamilies in the SOS Response system. We present evidence that one of these, the SOS Response associated peptidase (SRAP; Pfam: DUF159) is a novel thiol autopeptidase. Given the involvement of other autopeptidases, such as LexA and UmuD, in the SOS Response, this finding suggests that multiple structurally unrelated peptidases have been recruited to this process. The second of these, the ImuB-C superfamily, is linked to the Y-family DNA polymerase-related domain in ImuB, and also occurs as a standalone protein. We present evidence using gene neighborhood analysis that both these domains function with different mutagenic polymerases in bacteria, such as Pol IV (DinB), Pol V (UmuCD) and ImuA-ImuB-DnaE2 and also other repair systems, which either deploy Ku and an ATP-dependent ligase or a SplB-like radical SAM photolyase. We suggest that the SRAP superfamily domain functions as a DNA-associated autoproteolytic switch that recruits diverse repair enzymes upon DNA damage, whereas the ImuB-C domain performs a similar function albeit in a non-catalytic fashion. We propose that C3Orf37, the eukaryotic member of the SRAP superfamily, which h as been recently shown to specifically bind DNA with 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine, is a sensor for these oxidized bases generated by the TET enzymes from methylcytosine. Hence, its autoproteolytic activity might help it act as a switch that recruits DNA repair enzymes to remove these oxidized methylcytosine species as part of the DNA demethylation pathway downstream of the TET enzymes. Reviewers: This article was reviewed by RDS, RF and GJ.
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novel autoproteolytic and dna damage sensing components in the bacterial SOS Response and oxidized methylcytosine induced eukaryotic dna demethylation systems
Biology Direct, 2013Co-Authors: L Aravind, Swadha Anand, Lakshminarayan M IyerAbstract:The bacterial SOS Response is an elaborate program for DNA repair, cell cycle regulation and adaptive mutagenesis under stress conditions. Using sensitive sequence and structure analysis, combined with contextual information derived from comparative genomics and domain architectures, we identify two novel domain superfamilies in the SOS Response system. We present evidence that one of these, the SOS Response associated peptidase (SRAP; Pfam: DUF159) is a novel thiol autopeptidase. Given the involvement of other autopeptidases, such as LexA and UmuD, in the SOS Response, this finding suggests that multiple structurally unrelated peptidases have been recruited to this process. The second of these, the ImuB-C superfamily, is linked to the Y-family DNA polymerase-related domain in ImuB, and also occurs as a standalone protein. We present evidence using gene neighborhood analysis that both these domains function with different mutagenic polymerases in bacteria, such as Pol IV (DinB), Pol V (UmuCD) and ImuA-ImuB-DnaE2 and also other repair systems, which either deploy Ku and an ATP-dependent ligase or a SplB-like radical SAM photolyase. We suggest that the SRAP superfamily domain functions as a DNA-associated autoproteolytic switch that recruits diverse repair enzymes upon DNA damage, whereas the ImuB-C domain performs a similar function albeit in a non-catalytic fashion. We propose that C3Orf37, the eukaryotic member of the SRAP superfamily, which has been recently shown to specifically bind DNA with 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine, is a sensor for these oxidized bases generated by the TET enzymes from methylcytosine. Hence, its autoproteolytic activity might help it act as a switch that recruits DNA repair enzymes to remove these oxidized methylcytosine species as part of the DNA demethylation pathway downstream of the TET enzymes. This article was reviewed by RDS, RF and GJ.
