scholarly journals Probing the role of active site loops in E. coli Y family DNA damage bypass polymerase V

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Lisa A Hawver ◽  
Caitlin Gillooly ◽  
Penny J Beuning
Keyword(s):  
Dna Damage ◽  
Active Site ◽  
E Coli ◽  
Y Family ◽  
Bypass Polymerase

Effects of Plasma Kallikrein Specific Inhibitor and Active-site Blocked Factor VIIa on the Pulmonary Vascular Injury Induced by Endotoxin in Rats

1997 ◽  
Vol 78 (04) ◽  
pp. 1209-1214 ◽  
Author(s):  
Mitsuhiro Uchiba ◽  
Kenji Okajima ◽  
Kazunori Murakami ◽  
Hiroaki Okabe ◽  
Shosuke Okamoto ◽  
...  
Keyword(s):  
Vascular Injury ◽  
Active Site ◽  
Factor Viia ◽  
Specific Inhibitor ◽  
Coagulation System ◽  
Plasma Kallikrein ◽  
Extrinsic Pathway ◽  
E Coli ◽  
Intravascular Coagulation

SummaryThe acute respiratory distress syndrome (ARDS) is a serious complication of sepsis. To evaluate the role of the coagulation system in the pathogenesis of ARDS in sepsis, we examined the effects of the administration of a synthetic plasma kallikrein specific inhibitor (PKSI) and of active-site blocked factor VIIa (DEGR-VIIa) on the pulmonary vascular injury induced by E. coli endotoxin (ET) in rats. Administration of PKSI prevented the pulmonary vascular injury induced by ET as well as pulmonary histological changes in animals administered ET, but it did not affect the intravascular coagulation. The opposite effect was seen with DEGR-VIIa, which prevented the intravascular coagulation but not the pulmonary vascular injury. PKSI did not inhibit the activation of the complement system induced by ET leading to the activation of neutrophils.Findings suggest that PKSI may prevent the pulmonary vascular injury induced by ET by inhibiting kallikrein, which activates the neutrophils. The intrinsic pathway of coagulation may be more important than the extrinsic pathway in the pulmonary vascular injury produced byET.

scholarly journals The Roles of UmuD in Regulating Mutagenesis

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Jaylene N. Ollivierre ◽  
Jing Fang ◽  
Penny J. Beuning
Keyword(s):  
Dna Damage ◽  
Protein Interactions ◽  
Dna Polymerases ◽  
Gene Products ◽  
E Coli ◽  
Domains Of Life ◽  
Induced Mutagenesis ◽  
Multiple Conformations ◽  
Y Family ◽  
Damaged Dna

All organisms are subject to DNA damage from both endogenous and environmental sources. DNA damage that is not fully repaired can lead to mutations. Mutagenesis is now understood to be an active process, in part facilitated by lower-fidelity DNA polymerases that replicate DNA in an error-prone manner. Y-family DNA polymerases, found throughout all domains of life, are characterized by their lower fidelity on undamaged DNA and their specialized ability to copy damaged DNA. TwoE. coliY-family DNA polymerases are responsible for copying damaged DNA as well as for mutagenesis. These DNA polymerases interact with different forms of UmuD, a dynamic protein that regulates mutagenesis. The UmuD gene products, regulated by the SOS response, exist in two principal forms:UmuD2, which prevents mutagenesis, andUmuD2′, which facilitates UV-induced mutagenesis. This paper focuses on the multiple conformations of the UmuD gene products and how their protein interactions regulate mutagenesis.

Role of Active Site Loop Dynamics in Mediating Ligand Release from E. coli Dihydrofolate Reductase

Biochemistry ◽  
2021 ◽  
Author(s):  
Amrinder Singh ◽  
R. Bryn Fenwick ◽  
H. Jane Dyson ◽  
Peter E. Wright
Keyword(s):  
Dihydrofolate Reductase ◽  
Active Site ◽  
E Coli ◽  
Loop Dynamics

scholarly journals Separate Domains of Rev1 Mediate Two Modes of DNA Damage Bypass in Mammalian Cells

2009 ◽  
Vol 29 (11) ◽  
pp. 3113-3123 ◽  
Author(s):  
Jacob G. Jansen ◽  
Anastasia Tsaalbi-Shtylik ◽  
Giel Hendriks ◽  
Himabindu Gali ◽  
Ayal Hendel ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mammalian Cells ◽  
Uv Light ◽  
Brct Domain ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Dna Damage Signaling ◽  
Dna Damage Responses ◽  
Y Family

ABSTRACT The Y family DNA polymerase Rev1 has been proposed to play a regulatory role in the replication of damaged templates. To elucidate the mechanism by which Rev1 promotes DNA damage bypass, we have analyzed the progression of replication on UV light-damaged DNA in mouse embryonic fibroblasts that contain a defined deletion in the N-terminal BRCT domain of Rev1 or that are deficient for Rev1. We provide evidence that Rev1 plays a coordinating role in two modes of DNA damage bypass, i.e., an early and a late pathway. The cells carrying the deletion in the BRCT domain are deficient for the early pathway, reflecting a role of the BRCT domain of Rev1 in mutagenic translesion synthesis. Rev1-deficient cells display a defect in both modes of DNA damage bypass. Despite the persistent defect in the late replicational bypass of fork-blocking (6-4)pyrimidine-pyrimidone photoproducts, overall replication is not strongly affected by Rev1 deficiency. This results in almost completely replicated templates that contain gaps encompassing the photoproducts. These gaps are inducers of DNA damage signaling leading to an irreversible G2 arrest. Our results corroborate a model in which Rev1-mediated DNA damage bypass at postreplicative gaps quenches irreversible DNA damage responses.

On the catalytic role of the active site residue E121 of E. coli l-aspartate oxidase

Biochimie ◽  
2010 ◽  
Vol 92 (10) ◽  
pp. 1335-1342 ◽  
Author(s):  
Gabriella Tedeschi ◽  
Simona Nonnis ◽  
Bice Strumbo ◽  
Gabriele Cruciani ◽  
Emanuele Carosati ◽  
...  
Keyword(s):  
Active Site ◽  
Active Site Residue ◽  
E Coli ◽  
Catalytic Role

scholarly journals Colibactin-Producing Escherichia coli Induce the Formation of Invasive Carcinomas in a Chronic Inflammation-Associated Mouse Model

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2060
Author(s):  
Laurène Salesse ◽  
Cécily Lucas ◽  
My Hanh Thi Hoang ◽  
Pierre Sauvanet ◽  
Alexandra Rezard ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Mouse Model ◽  
Genetic Susceptibility ◽  
Colorectal Carcinogenesis ◽  
Intestinal Epithelial ◽  
E Coli ◽  
Invasive Carcinomas ◽  
Damage Marker

Background: Escherichia coli producing the genotoxin colibactin (CoPEC or colibactin-producing E. coli) abnormally colonize the colonic mucosa of colorectal cancer (CRC) patients. We previously showed that deficiency of autophagy in intestinal epithelial cells (IECs) enhances CoPEC-induced colorectal carcinogenesis in ApcMin/+ mice. Here, we tested if CoPEC trigger tumorigenesis in a mouse model lacking genetic susceptibility or the use of carcinogen. Methods: Mice with autophagy deficiency in IECs (Atg16l1∆IEC) or wild-type mice (Atg16l1flox/flox) were infected with the CoPEC 11G5 strain or the mutant 11G5∆clbQ incapable of producing colibactin and subjected to 12 cycles of DSS treatment to induce chronic colitis. Mouse colons were used for histological assessment, immunohistochemical and immunoblot analyses for DNA damage marker. Results: 11G5 or 11G5∆clbQ infection increased clinical and histological inflammation scores, and these were further enhanced by IEC-specific autophagy deficiency. 11G5 infection, but not 11G5∆clbQ infection, triggered the formation of invasive carcinomas, and this was further increased by autophagy deficiency. The increase in invasive carcinomas was correlated with enhanced DNA damage and independent of inflammation. Conclusions: CoPEC induce colorectal carcinogenesis in a CRC mouse model lacking genetic susceptibility and carcinogen. This work highlights the role of (i) CoPEC as a driver of CRC development, and (ii) autophagy in inhibiting the carcinogenic properties of CoPEC.

Role of the Y-Family DNA Polymerases YqjH and YqjW in Protecting Sporulating Bacillus subtilis Cells from DNA Damage

2009 ◽  
Vol 60 (4) ◽  
pp. 263-267 ◽  
Author(s):  
Andrea M. Rivas-Castillo ◽  
Ronald E. Yasbin ◽  
E. Robleto ◽  
Wayne L. Nicholson ◽  
Mario Pedraza-Reyes
Keyword(s):  
Dna Damage ◽  
Bacillus Subtilis ◽  
Dna Polymerases ◽  
Y Family

scholarly journals Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis in Escherichia coli

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e6029 ◽  
Author(s):  
Caroline Zutterling ◽  
Aibek Mursalimov ◽  
Ibtissam Talhaoui ◽  
Zhanat Koshenov ◽  
Zhiger Akishev ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Dna Repair ◽  
Uv Irradiation ◽  
Genome Stability ◽  
Dna Duplexes ◽  
E Coli ◽  
Dna Strands ◽  
Induced Mutagenesis

Background DNA repair is essential to counteract damage to DNA induced by endo- and exogenous factors, to maintain genome stability. However, challenges to the faithful discrimination between damaged and non-damaged DNA strands do exist, such as mismatched pairs between two regular bases resulting from spontaneous deamination of 5-methylcytosine or DNA polymerase errors during replication. To counteract these mutagenic threats to genome stability, cells evolved the mismatch-specific DNA glycosylases that can recognize and remove regular DNA bases in the mismatched DNA duplexes. The Escherichia coli adenine-DNA glycosylase (MutY/MicA) protects cells against oxidative stress-induced mutagenesis by removing adenine which is mispaired with 7,8-dihydro-8-oxoguanine (8oxoG) in the base excision repair pathway. However, MutY does not discriminate between template and newly synthesized DNA strands. Therefore the ability to remove A from 8oxoG•A mispair, which is generated via misincorporation of an 8-oxo-2′-deoxyguanosine-5′-triphosphate precursor during DNA replication and in which A is the template base, can induce A•T→C•G transversions. Furthermore, it has been demonstrated that human MUTYH, homologous to the bacterial MutY, might be involved in the aberrant processing of ultraviolet (UV) induced DNA damage. Methods Here, we investigated the role of MutY in UV-induced mutagenesis in E. coli. MutY was probed on DNA duplexes containing cyclobutane pyrimidine dimers (CPD) and pyrimidine (6–4) pyrimidone photoproduct (6–4PP). UV irradiation of E. coli induces Save Our Souls (SOS) response characterized by increased production of DNA repair enzymes and mutagenesis. To study the role of MutY in vivo, the mutation frequencies to rifampicin-resistant (RifR) after UV irradiation of wild type and mutant E. coli strains were measured. Results We demonstrated that MutY does not excise Adenine when it is paired with CPD and 6–4PP adducts in duplex DNA. At the same time, MutY excises Adenine in A•G and A•8oxoG mispairs. Interestingly, E. coli mutY strains, which have elevated spontaneous mutation rate, exhibited low mutational induction after UV exposure as compared to MutY-proficient strains. However, sequence analysis of RifR mutants revealed that the frequencies of C→T transitions dramatically increased after UV irradiation in both MutY-proficient and -deficient E. coli strains. Discussion These findings indicate that the bacterial MutY is not involved in the aberrant DNA repair of UV-induced DNA damage.

scholarly journals Mutational analysis of DinG-family helicase YoaA: its expression and interaction with replication clamp-loader protein HolC in E. coli

2021 ◽  
Author(s):  
Vincent A. Sutera ◽  
Thalia H. Sass ◽  
Scott E. Leonard ◽  
Lingling Wu ◽  
David J. Glass ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mutational Analysis ◽  
Physical Interaction ◽  
Clamp Loader ◽  
Dna Helicases ◽  
E Coli ◽  
C Terminus ◽  
Damage Response ◽  
Domains Of Life

ABSTRACTThe XP-D/DinG family of DNA helicases participate in a variety of ways to preserve genomic stability in all three domains of life. We investigate here the genetic role of one of these proteins,YoaA, of Escherichia coli. In E. coli,YoaA has been identified as having a role in tolerance to the nucleoside azidothymidine (AZT), a DNA replication inhibitor. It is of particular interest because of its physical interaction with a component of the DNA polymerase III holoenzyme, HolC (or χ). We have proposed that this interaction competes with HolC’s interaction with HolD (or ψ) and the rest of the replisome. In this work, we map the residues of YoaA that are required for HolC interaction to the C-terminus of the protein by yeast two-hybrid analysis. We also confirm by gene fusions that YoaA is induced as part of the SOS response to DNA damage and define an upstream “LexA box” sequence in its regulation. Induction of YoaA by AZT is biphasic throughout growth of the culture with an immediate response after treatment and a slower response that peaks in the late log phase of growth. This growth-phase dependent induction by AZT is not blocked by the lexA3 (Ind-) allele, which normally negates its self-cleavage, implying another means to induce the DNA damage response that responds to the nutritional state of the cell.

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