LIVIVO - Search results -

Search results

Result 1 - 10 of total 93

Search options

Article ; Online: A catch and release program for single-stranded DNA.

Eoff, Robert L / Raney, Kevin D

2017 Volume 292, Issue 31, Page(s) 13085–13086

Abstract: Uncovering the mechanisms by which single-stranded binding proteins both protect and expose single-stranded DNA has important implications for our understanding of DNA replication and repair. A new study serves up a master class in developing a full ... ...

Abstract	Uncovering the mechanisms by which single-stranded binding proteins both protect and expose single-stranded DNA has important implications for our understanding of DNA replication and repair. A new study serves up a master class in developing a full kinetic model for one such protein, mtSSB, showing how DNA can be reeled in and set free to control accessibility.
MeSH term(s)	Binding Sites ; DNA Repair ; DNA Replication ; DNA, Mitochondrial/chemistry ; DNA, Mitochondrial/metabolism ; DNA, Single-Stranded/chemistry ; DNA, Single-Stranded/metabolism ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/metabolism ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/metabolism ; Humans ; Kinetics ; Mitochondrial Proteins/chemistry ; Mitochondrial Proteins/metabolism ; Models, Molecular ; Protein Multimerization
Chemical Substances	DNA, Mitochondrial ; DNA, Single-Stranded ; DNA-Binding Proteins ; Escherichia coli Proteins ; Mitochondrial Proteins ; SSB protein, E coli ; SSBP1 protein, human
Language	English
Publishing date	2017-07-14
Publishing country	United States
Document type	Comparative Study ; Editorial ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.H117.791392
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Translesion DNA Synthesis in Cancer: Molecular Mechanisms and Therapeutic Opportunities.

Zafar, Maroof K / Eoff, Robert L

Chemical research in toxicology

2017 Volume 30, Issue 11, Page(s) 1942–1955

Abstract: The genomic landscape of cancer is one marred by instability, but the mechanisms that underlie these alterations are multifaceted and remain a topic of intense research. Cellular responses to DNA damage and/or replication stress can affect genome ... ...

Abstract	The genomic landscape of cancer is one marred by instability, but the mechanisms that underlie these alterations are multifaceted and remain a topic of intense research. Cellular responses to DNA damage and/or replication stress can affect genome stability in tumors and influence the response of patients to therapy. In addition to direct repair, DNA damage tolerance (DDT) is an element of genomic maintenance programs that contributes to the etiology of several types of cancer. DDT mechanisms primarily act to resolve replication stress, and this can influence the effectiveness of genotoxic drugs. Translesion DNA synthesis (TLS) is an important component of DDT that facilitates direct bypass of DNA adducts and other barriers to replication. The central role of TLS in the bypass of drug-induced DNA lesions, the promotion of tumor heterogeneity, and the involvement of these enzymes in the maintenance of the cancer stem cell niche presents an opportunity to leverage inhibition of TLS as a way of improving existing therapies. In the review that follows, we summarize mechanisms of DDT, misregulation of TLS in cancer, and discuss the potential for targeting these pathways as a means of improving cancer therapies.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; DNA/genetics ; DNA Damage/drug effects ; DNA Repair/drug effects ; DNA Replication/drug effects ; Humans ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/genetics ; Signal Transduction/drug effects
Chemical Substances	Antineoplastic Agents ; DNA (9007-49-2)
Language	English
Publishing date	2017-09-28
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	639353-6
ISSN	1520-5010 ; 0893-228X
ISSN (online)	1520-5010
ISSN	0893-228X
DOI	10.1021/acs.chemrestox.7b00157
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2320: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: A Facile Semisynthesis and Evaluation of Garcinoic Acid and Its Analogs for the Inhibition of Human DNA Polymerase β.

Gujarathi, Satheesh / Zafar, Maroof Khan / Liu, Xingui / Eoff, Robert L / Zheng, Guangrong

Molecules (Basel, Switzerland)

2020 Volume 25, Issue 24

Abstract: Garcinoic acid has been identified as an inhibitor of DNA polymerase β (pol β). However, no structure-activity relationship (SAR) studies of garcinoic acid as a pol β inhibitor have been conducted, in part due to the lack of an efficient synthetic method ...

Abstract	Garcinoic acid has been identified as an inhibitor of DNA polymerase β (pol β). However, no structure-activity relationship (SAR) studies of garcinoic acid as a pol β inhibitor have been conducted, in part due to the lack of an efficient synthetic method for this natural product and its analogs. We developed an efficient semi-synthetic method for garcinoic acid and its analogs by starting from natural product δ-tocotrienol. Our preliminary SAR studies provided a valuable insight into future discovery of garcinoic acid-based pol β inhibitors.
MeSH term(s)	Benzopyrans/chemical synthesis ; Biological Products/chemistry ; Chemistry Techniques, Synthetic ; DNA Polymerase beta/antagonists & inhibitors ; Drug Design ; Enzyme Inhibitors/chemical synthesis ; Humans ; Inhibitory Concentration 50 ; Phenol/chemistry ; Structure-Activity Relationship ; Temperature ; Vitamin E/analogs & derivatives ; Vitamin E/chemistry
Chemical Substances	Benzopyrans ; Biological Products ; Enzyme Inhibitors ; garcinoic acid ; Vitamin E (1406-18-4) ; tocotrienol, delta (1SRB74OWSI) ; Phenol (339NCG44TV) ; DNA Polymerase beta (EC 2.7.7.7) ; POLB protein, human (EC 2.7.7.7)
Language	English
Publishing date	2020-12-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules25245847
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.MO 81: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Conservation of the insert-2 motif confers Rev1 from different species with an ability to disrupt G-quadruplexes and stimulate translesion DNA synthesis.

Ketkar, Amit / Sewilam, Reham S / McCrury, Mason J / Hall, Jaycelyn S / Bell, Ashtyn / Paxton, Bethany C / Tripathi, Shreyam / Gunderson, Julie E C / Eoff, Robert L

RSC chemical biology

2023 Volume 4, Issue 7, Page(s) 466–485

Abstract: In some organisms, the replication of G-quadruplex (G4) structures is supported by the Rev1 DNA polymerase. We previously showed that residues in the insert-2 motif of human Rev1 (hRev1) increased the affinity of the enzyme for G4 DNA and mediated ... ...

Abstract	In some organisms, the replication of G-quadruplex (G4) structures is supported by the Rev1 DNA polymerase. We previously showed that residues in the insert-2 motif of human Rev1 (hRev1) increased the affinity of the enzyme for G4 DNA and mediated suppression of mutagenic replication near G4 motifs. We have now investigated the conservation of G4-selective properties in Rev1 from other species. We compared Rev1 from
Language	English
Publishing date	2023-05-11
Publishing country	England
Document type	Journal Article
ISSN	2633-0679
ISSN (online)	2633-0679
DOI	10.1039/d3cb00027c
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Inhibition of tryptophan 2,3-dioxygenase impairs DNA damage tolerance and repair in glioma cells.

Reed, Megan R / Maddukuri, Leena / Ketkar, Amit / Byrum, Stephanie D / Zafar, Maroof K / Bostian, April C L / Tackett, Alan J / Eoff, Robert L

NAR cancer

2021 Volume 3, Issue 2, Page(s) zcab014

Abstract: Expression of tryptophan 2,3-dioxygenase (TDO) is a determinant of malignancy in gliomas through kynurenine (KYN) signaling. We report that inhibition of TDO activity attenuated recovery from replication stress and increased the genotoxic effects of bis- ... ...

Abstract	Expression of tryptophan 2,3-dioxygenase (TDO) is a determinant of malignancy in gliomas through kynurenine (KYN) signaling. We report that inhibition of TDO activity attenuated recovery from replication stress and increased the genotoxic effects of bis-chloroethylnitrosourea (BCNU). Activation of the Chk1 arm of the replication stress response (RSR) was reduced when TDO activity was blocked prior to BCNU treatment, whereas phosphorylation of serine 33 (pS33) on replication protein A (RPA) was enhanced-indicative of increased fork collapse. Analysis of quantitative proteomic results revealed that TDO inhibition reduced nuclear 53BP1 and sirtuin levels. We confirmed that cells lacking TDO activity exhibited elevated gamma-H2AX signal and defective recruitment of 53BP1 to chromatin following BCNU treatment, which corresponded with delayed repair of DNA breaks. Addition of exogenous KYN increased the rate of break repair. TDO inhibition diminished SIRT7 deacetylase recruitment to chromatin, which increased histone H3K18 acetylation-a key mark involved in preventing 53BP1 recruitment to sites of DNA damage. TDO inhibition also sensitized cells to ionizing radiation (IR)-induced damage, but this effect did not involve altered 53BP1 recruitment. These experiments support a model where TDO-mediated KYN signaling helps fuel a robust response to replication stress and DNA damage.
Language	English
Publishing date	2021-04-09
Publishing country	England
Document type	Journal Article
ISSN	2632-8674
ISSN (online)	2632-8674
DOI	10.1093/narcan/zcab014
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- Full text online
- Order with fees

Article ; Online: Aberrant Kynurenine Signaling Modulates DNA Replication Stress Factors and Promotes Genomic Instability in Gliomas.

Bostian, April C L / Eoff, Robert L

Chemical research in toxicology

2016 Volume 29, Issue 9, Page(s) 1369–1380

Abstract: Metabolism of the essential amino acid L-tryptophan (TRP) is implicated in a number of neurological conditions including depression, neurodegenerative diseases, and cancer. The TRP catabolite kynurenine (KYN) has recently emerged as an important ... ...

Abstract	Metabolism of the essential amino acid L-tryptophan (TRP) is implicated in a number of neurological conditions including depression, neurodegenerative diseases, and cancer. The TRP catabolite kynurenine (KYN) has recently emerged as an important neuroactive factor in brain tumor pathogenesis, with additional studies implicating KYN in other types of cancer. Often highlighted as a modulator of the immune response and a contributor to immune escape for malignant tumors, it is well-known that KYN has effects on the production of the coenzyme nicotinamide adenine dinucleotide (NAD(+)), which can have a direct impact on DNA repair, replication, cell division, redox signaling, and mitochondrial function. Additional effects of KYN signaling are imparted through its role as an endogenous agonist for the aryl hydrocarbon receptor (AhR), and it is largely through activation of the AhR that KYN appears to mediate malignant progression in gliomas. We have recently reported on the ability of KYN signaling to modulate expression of human DNA polymerase kappa (hpol κ), a translesion enzyme involved in bypass of bulky DNA lesions and activation of the replication stress response. Given the impact of KYN on NAD(+) production, AhR signaling, and translesion DNA synthesis, it follows that dysregulation of KYN signaling in cancer may promote malignancy through alterations in the level of endogenous DNA damage and replication stress. In this perspective, we discuss the connections between KYN signaling, DNA damage tolerance, and genomic instability, as they relate to cancer.
MeSH term(s)	DNA Replication/physiology ; Genomic Instability/physiology ; Glioma/physiopathology ; Humans ; Kynurenine/physiology ; Neoplasms/physiopathology ; Signal Transduction/physiology
Chemical Substances	Kynurenine (343-65-7)
Language	English
Publishing date	2016-09-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	639353-6
ISSN	1520-5010 ; 0893-228X
ISSN (online)	1520-5010
ISSN	0893-228X
DOI	10.1021/acs.chemrestox.6b00255
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2320: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Residues in the RecQ C-terminal Domain of the Human Werner Syndrome Helicase Are Involved in Unwinding G-quadruplex DNA.

Ketkar, Amit / Voehler, Markus / Mukiza, Tresor / Eoff, Robert L

The Journal of biological chemistry

2017 Volume 292, Issue 8, Page(s) 3154–3163

Abstract: The structural and biophysical properties typically associated with G-quadruplex (G4) structures render them a significant block for DNA replication, which must be overcome for cell division to occur. The Werner syndrome protein (WRN) is a RecQ family ... ...

Abstract	The structural and biophysical properties typically associated with G-quadruplex (G4) structures render them a significant block for DNA replication, which must be overcome for cell division to occur. The Werner syndrome protein (WRN) is a RecQ family helicase that has been implicated in the efficient processing of G4 DNA structures. The aim of this study was to identify the residues of WRN involved in the binding and ATPase-driven unwinding of G4 DNA. Using a c-Myc G4 DNA model sequence and recombinant WRN, we have determined that the RecQ-C-terminal (RQC) domain of WRN imparts a 2-fold preference for binding to G4 DNA relative to non-G4 DNA substrates. NMR studies identified residues involved specifically in interactions with G4 DNA. Three of the amino acids in the WRN RQC domain that exhibited the largest G4-specific changes in NMR signal were then mutated alone or in combination. Mutating individual residues implicated in G4 binding had a modest effect on WRN binding to DNA, decreasing the preference for G4 substrates by ∼25%. Mutating two G4-interacting residues (T1024G and T1086G) abrogated preferential binding of WRN to G4 DNA. Very modest decreases in G4 DNA-stimulated ATPase activity were observed for the mutant enzymes. Most strikingly, G4 unwinding by WRN was inhibited ∼50% for all three point mutants and >90% for the WRN double mutant (T1024G/T1086G) relative to normal B-form dsDNA substrates. Our work has helped to identify residues in the WRN RQC domain that are involved specifically in the interaction with G4 DNA.
MeSH term(s)	DNA/chemistry ; DNA/genetics ; DNA/metabolism ; DNA Repair ; DNA Replication ; G-Quadruplexes ; Humans ; Models, Molecular ; Mutation ; Protein Domains ; Werner Syndrome/enzymology ; Werner Syndrome/genetics ; Werner Syndrome/metabolism ; Werner Syndrome Helicase/chemistry ; Werner Syndrome Helicase/genetics ; Werner Syndrome Helicase/metabolism
Chemical Substances	DNA (9007-49-2) ; Werner Syndrome Helicase (EC 3.6.4.12)
Language	English
Publishing date	2017-01-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M116.767699
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Kinetic mechanism for DNA unwinding by multiple molecules of Dda helicase aligned on DNA.

Eoff, Robert L / Raney, Kevin D

Biochemistry

2010 Volume 49, Issue 21, Page(s) 4543–4553

Abstract: Helicases catalyze the separation of double-stranded nucleic acids to form single-stranded intermediates. Using transient state kinetic methods, we have determined the kinetic properties of DNA unwinding under conditions that favor a monomeric form of ... ...

Abstract	Helicases catalyze the separation of double-stranded nucleic acids to form single-stranded intermediates. Using transient state kinetic methods, we have determined the kinetic properties of DNA unwinding under conditions that favor a monomeric form of the Dda helicase as well as conditions that allow multiple molecules to function on the same substrate. Multiple helicase molecules can align like a train on the DNA track. The number of base pairs unwound in a single binding event for Dda is increased from approximately 19 bp for the monomeric form to approximately 64 bp when as many as four Dda molecules are aligned on the same substrate, while the kinetic step size (3.2 +/- 0.7 bp) and unwinding rate (242 +/- 25 bp/s) appear to be independent of the number of Dda molecules present on a given substrate. The data support a model in which the helicase molecules bound to the same substrate move along the DNA track independently during DNA unwinding. The observed increase in processivity arises from the increased probability that at least one of the helicases will completely unwind the DNA prior to dissociation. These results are in contrast to previous reports in which multiple Dda molecules on the same track greatly enhanced the rate and amplitude for displacement of protein blocks on the track. Therefore, only when the progress of the lead molecule in the train is impeded by some type of block, such as a protein bound to DNA, do the trailing molecules interact with the lead molecule to overcome the block. The fact that trailing helicase molecules have little impact on the lead molecule in the train during routine DNA unwinding suggests that the trailing molecules are moving at rates similar to that of the lead molecule. This result implicates a step in the translocation mechanism as contributing greatly to the overall rate-limiting step for unwinding of duplex DNA.
MeSH term(s)	Base Pairing ; Catalysis ; DNA/chemistry ; DNA/genetics ; DNA/metabolism ; DNA Helicases/genetics ; DNA Helicases/metabolism ; DNA, Single-Stranded/chemistry ; DNA, Single-Stranded/genetics ; DNA, Single-Stranded/metabolism
Chemical Substances	DNA, Single-Stranded ; DNA (9007-49-2) ; DNA Helicases (EC 3.6.4.-)
Language	English
Publishing date	2010-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/bi100061v
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 217: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Biobanked Glioblastoma Patient-Derived Organoids as a Precision Medicine Model to Study Inhibition of Invasion.

Darrigues, Emilie / Zhao, Edward H / De Loose, Annick / Lee, Madison P / Borrelli, Michael J / Eoff, Robert L / Galileo, Deni S / Penthala, Narsimha R / Crooks, Peter A / Rodriguez, Analiz

International journal of molecular sciences

2021 Volume 22, Issue 19

Abstract: Glioblastoma (GBM) is highly resistant to treatment and invasion into the surrounding brain is a cancer hallmark that leads to recurrence despite surgical resection. With the emergence of precision medicine, patient-derived 3D systems are considered ... ...

Abstract	Glioblastoma (GBM) is highly resistant to treatment and invasion into the surrounding brain is a cancer hallmark that leads to recurrence despite surgical resection. With the emergence of precision medicine, patient-derived 3D systems are considered potentially robust GBM preclinical models. In this study, we screened a library of 22 anti-invasive compounds (i.e., NF-kB, GSK-3-B, COX-2, and tubulin inhibitors) using glioblastoma U-251 MG cell spheroids. We evaluated toxicity and invasion inhibition using a 3D Matrigel invasion assay. We next selected three compounds that inhibited invasion and screened them in patient-derived glioblastoma organoids (GBOs). We developed a platform using available macros for FIJI/ImageJ to quantify invasion from the outer margin of organoids. Our data demonstrated that a high-throughput invasion screening can be done using both an established cell line and patient-derived 3D model systems. Tubulin inhibitor compounds had the best efficacy with U-251 MG cells, however, in ex vivo patient organoids the results were highly variable. Our results indicate that the efficacy of compounds is highly related to patient intra and inter-tumor heterogeneity. These results indicate that such models can be used to evaluate personal oncology therapeutic strategies.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Biological Specimen Banks ; Brain Neoplasms/drug therapy ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Drug Discovery/methods ; Drug Screening Assays, Antitumor/methods ; Glioblastoma/drug therapy ; Glioblastoma/pathology ; Humans ; Neoplasm Invasiveness ; Organoids ; Precision Medicine/methods ; Spheroids, Cellular ; Tissue Culture Techniques
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2021-10-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms221910720
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Human Rev1 relies on insert-2 to promote selective binding and accurate replication of stabilized G-quadruplex motifs.

Ketkar, Amit / Smith, Lane / Johnson, Callie / Richey, Alyssa / Berry, Makayla / Hartman, Jessica H / Maddukuri, Leena / Reed, Megan R / Gunderson, Julie E C / Leung, Justin W C / Eoff, Robert L

Nucleic acids research

2021 Volume 49, Issue 4, Page(s) 2065–2084

Abstract: We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 motifs, finding that hRev1 exhibited stronger affinity for ... ...

Abstract	We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 motifs, finding that hRev1 exhibited stronger affinity for parallel-stranded G4 than either anti-parallel or hybrid folds. Amino acids in the αE helix of insert-2 were identified as being important for G4 binding. Mutating E466 and Y470 to alanine selectively perturbed G4 binding affinity. The E466K mutant restored wild-type G4 binding properties. Using a forward mutagenesis assay, we discovered that loss of hRev1 increased G4 mutation frequency >200-fold compared to the control sequence. Base substitutions and deletions occurred around and within the G4 motif. Pyridostatin (PDS) exacerbated this effect, as the mutation frequency increased >700-fold over control and deletions upstream of the G4 site more than doubled. Mutagenic replication of G4 DNA (±PDS) was partially rescued by wild-type and E466K hRev1. The E466A or Y470A mutants failed to suppress the PDS-induced increase in G4 mutation frequency. These findings have implications for the role of insert-2, a motif conserved in vertebrates but not yeast or plants, in Rev1-mediated suppression of mutagenesis during G4 replication.
MeSH term(s)	Cell Line ; DNA/chemistry ; DNA/metabolism ; DNA Replication ; DNA-Directed DNA Polymerase/metabolism ; G-Quadruplexes ; Genes, myc ; Humans ; Models, Molecular ; Mutation ; Nucleotide Motifs ; Nucleotidyltransferases/chemistry ; Nucleotidyltransferases/genetics ; Nucleotidyltransferases/metabolism ; Protein Binding
Chemical Substances	DNA (9007-49-2) ; Nucleotidyltransferases (EC 2.7.7.-) ; REV1 protein, human (EC 2.7.7.-) ; DNA-Directed DNA Polymerase (EC 2.7.7.7)
Language	English
Publishing date	2021-02-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkab041
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1067: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito