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Article: Therapy-associated remodeling of pancreatic cancer revealed by single-cell spatial transcriptomics and optimal transport analysis.

Shiau, Carina / Cao, Jingyi / Gregory, Mark T / Gong, Dennis / Yin, Xunqin / Cho, Jae-Won / Wang, Peter L / Su, Jennifer / Wang, Steven / Reeves, Jason W / Kim, Tae Kyung / Kim, Youngmi / Guo, Jimmy A / Lester, Nicole A / Schurman, Nathan / Barth, Jamie L / Weissleder, Ralph / Jacks, Tyler / Qadan, Motaz /

Hong, Theodore S / Wo, Jennifer Y / Roberts, Hannah / Beechem, Joseph M / Castillo, Carlos Fernandez-Del / Mino-Kenudson, Mari / Ting, David T / Hemberg, Martin / Hwang, William L

bioRxiv : the preprint server for biology

2023

Abstract: In combination with cell intrinsic properties, interactions in the tumor microenvironment modulate therapeutic response. We leveraged high-plex single-cell spatial transcriptomics to dissect the remodeling of multicellular neighborhoods and cell-cell ... ...

Abstract	In combination with cell intrinsic properties, interactions in the tumor microenvironment modulate therapeutic response. We leveraged high-plex single-cell spatial transcriptomics to dissect the remodeling of multicellular neighborhoods and cell-cell interactions in human pancreatic cancer associated with specific malignant subtypes and neoadjuvant chemotherapy/radiotherapy. We developed Spatially Constrained Optimal Transport Interaction Analysis (SCOTIA), an optimal transport model with a cost function that includes both spatial distance and ligand-receptor gene expression. Our results uncovered a marked change in ligand-receptor interactions between cancer-associated fibroblasts and malignant cells in response to treatment, which was supported by orthogonal datasets, including an
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.28.546848
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Article: Spatial analysis of human lung cancer reveals organized immune hubs enriched for stem-like CD8 T cells and associated with immunotherapy response.

Chen, Jonathan H / Nieman, Linda T / Spurrell, Maxwell / Jorgji, Vjola / Richieri, Peter / Xu, Katherine H / Madhu, Roopa / Parikh, Milan / Zamora, Izabella / Mehta, Arnav / Nabel, Christopher S / Freeman, Samuel S / Pirl, Joshua D / Lu, Chenyue / Meador, Catherine B / Barth, Jaimie L / Sakhi, Mustafa / Tang, Alexander L / Sarkizova, Siranush /

Price, Colles / Fernandez, Nicolas F / Emanuel, George / He, Jiang / Raay, Katrina Van / Reeves, Jason W / Yizhak, Keren / Hofree, Matan / Shih, Angela / Sade-Feldman, Moshe / Boland, Genevieve M / Pelka, Karin / Aryee, Martin / Korsunsky, Ilya / Mino-Kenudson, Mari / Gainor, Justin F / Hacohen, Nir

bioRxiv : the preprint server for biology

2023

Abstract: The organization of immune cells in human tumors is not well understood. Immunogenic tumors harbor spatially-localized multicellular 'immunity hubs' defined by expression of the T cell-attracting ... ...

Abstract	The organization of immune cells in human tumors is not well understood. Immunogenic tumors harbor spatially-localized multicellular 'immunity hubs' defined by expression of the T cell-attracting chemokines
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.04.535379
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Article ; Online: Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy.

Chen, Jonathan H / Nieman, Linda T / Spurrell, Maxwell / Jorgji, Vjola / Elmelech, Liad / Richieri, Peter / Xu, Katherine H / Madhu, Roopa / Parikh, Milan / Zamora, Izabella / Mehta, Arnav / Nabel, Christopher S / Freeman, Samuel S / Pirl, Joshua D / Lu, Chenyue / Meador, Catherine B / Barth, Jaimie L / Sakhi, Mustafa / Tang, Alexander L /

Sarkizova, Siranush / Price, Colles / Fernandez, Nicolas F / Emanuel, George / He, Jiang / Van Raay, Katrina / Reeves, Jason W / Yizhak, Keren / Hofree, Matan / Shih, Angela / Sade-Feldman, Moshe / Boland, Genevieve M / Pelka, Karin / Aryee, Martin J / Mino-Kenudson, Mari / Gainor, Justin F / Korsunsky, Ilya / Hacohen, Nir

Nature immunology

2024 Volume 25, Issue 4, Page(s) 644–658

Abstract: The organization of immune cells in human tumors is not well understood. Immunogenic tumors harbor spatially localized multicellular 'immunity hubs' defined by expression of the T cell-attracting chemokines CXCL10/CXCL11 and abundant T cells. Here, we ... ...

Abstract	The organization of immune cells in human tumors is not well understood. Immunogenic tumors harbor spatially localized multicellular 'immunity hubs' defined by expression of the T cell-attracting chemokines CXCL10/CXCL11 and abundant T cells. Here, we examined immunity hubs in human pre-immunotherapy lung cancer specimens and found an association with beneficial response to PD-1 blockade. Critically, we discovered the stem-immunity hub, a subtype of immunity hub strongly associated with favorable PD-1-blockade outcome. This hub is distinct from mature tertiary lymphoid structures and is enriched for stem-like TCF7
MeSH term(s)	Humans ; Lung Neoplasms ; CD8-Positive T-Lymphocytes ; Programmed Cell Death 1 Receptor ; Chemokines/metabolism ; Immunotherapy/methods ; Tumor Microenvironment
Chemical Substances	Programmed Cell Death 1 Receptor ; Chemokines
Language	English
Publishing date	2024-03-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-024-01792-2
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Article: Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb

Khan, Mona / Yoo, Seung-Jun / Clijsters, Marnick / Backaert, Wout / Vanstapel, Arno / Speleman, Kato / Lietaer, Charlotte / Choi, Sumin / Hether, Tyler D. / Marcelis, Lukas / Nam, Andrew / Pan, Liuliu / Reeves, Jason W. / Van Bulck, Pauline / Zhou, Hai / Bourgeois, Marc / Debaveye, Yves / De Munter, Paul / Gunst, Jan /

Jorissen, Mark / Lagrou, Katrien / Lorent, Natalie / Neyrinck, Arne / Peetermans, Marijke / Thal, Dietmar Rudolf / Vandenbriele, Christophe / Wauters, Joost / Mombaerts, Peter / Van Gerven, Laura

Cell. 2021 Nov. 24, v. 184, no. 24

2021

Abstract: Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to ... ...

Abstract	Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; mucosa ; olfactory bulb ; olfactory disorders ; smell ; surgery ; viruses
Language	English
Dates of publication	2021-1124
Size	p. 5932-5949.e15.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.10.027
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Article ; Online: Comprehensive analysis of cutaneous and uveal melanoma liver metastases.

Journal for immunotherapy of cancer

2020 Volume 8, Issue 2

Abstract: Background: The profound disparity in response to immune checkpoint blockade (ICB) by cutaneous melanoma (CM) and uveal melanoma (UM) patients is not well understood. Therefore, we characterized metastases of CM and UM from the same metastatic site ( ... ...

Abstract	Background: The profound disparity in response to immune checkpoint blockade (ICB) by cutaneous melanoma (CM) and uveal melanoma (UM) patients is not well understood. Therefore, we characterized metastases of CM and UM from the same metastatic site (liver), in order to dissect the potential underlying mechanism in differential response on ICB. Methods: Tumor liver samples from CM (n=38) and UM (n=28) patients were analyzed at the genomic (whole exome sequencing), transcriptional (RNA sequencing) and protein (immunohistochemistry and GeoMx Digital Spatial Profiling) level. Results: Comparison of CM and UM metastases from the same metastatic site revealed that, although originating from the same melanocyte lineage, CM and UM differed in somatic mutation profile, copy number profile, tumor mutational burden (TMB) and consequently predicted neoantigens. A higher melanin content and higher expression of the melanoma differentiation antigen MelanA was observed in liver metastases of UM patients. No difference in B2M and human leukocyte antigen-DR (HLA-DR) expression was observed. A higher expression of programmed cell death ligand 1 (PD-L1) was found in CM compared with UM liver metastases, although the majority of CM and UM liver metastases lacked PD-L1 expression. There was no difference in the extent of immune infiltration observed between CM and UM metastases, with the exception of a higher expression of CD163 (p<0.0001) in CM liver samples. While the extent of immune infiltration was similar for CM and UM metastases, the ratio of exhausted CD8 T cells to cytotoxic T cells, to total CD8 T cells and to Th1 cells, was significantly higher in UM metastases. Conclusions: While TMB was different between CM and UM metastases, tumor immune infiltration was similar. The greater dependency on PD-L1 as an immune checkpoint in CM and the identification of higher exhaustion ratios in UM may both serve as explanations for the difference in response to ICB. Consequently, in order to improve current treatment for metastatic UM, reversal of T cell exhaustion beyond programmed cell death 1 blockade should be considered.
MeSH term(s)	Female ; Humans ; Liver Neoplasms/secondary ; Male ; Melanoma/complications ; Melanoma/pathology ; Retrospective Studies ; Skin Neoplasms/complications ; Skin Neoplasms/pathology ; Uveal Neoplasms/complications ; Uveal Neoplasms/pathology ; Melanoma, Cutaneous Malignant
Language	English
Publishing date	2020-12-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2020-001501
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Article: Best Practices for Spatial Profiling for Breast Cancer Research with the GeoMx

Bergholtz, Helga / Carter, Jodi M / Cesano, Alessandra / Cheang, Maggie Chon U / Church, Sarah E / Divakar, Prajan / Fuhrman, Christopher A / Goel, Shom / Gong, Jingjing / Guerriero, Jennifer L / Hoang, Margaret L / Hwang, E Shelley / Kuasne, Hellen / Lee, Jinho / Liang, Yan / Mittendorf, Elizabeth A / Perez, Jessica / Prat, Aleix / Pusztai, Lajos /

Reeves, Jason W / Riazalhosseini, Yasser / Richer, Jennifer K / Sahin, Özgür / Sato, Hiromi / Schlam, Ilana / Sørlie, Therese / Stover, Daniel G / Swain, Sandra M / Swarbrick, Alexander / Thompson, E Aubrey / Tolaney, Sara M / Warren, Sarah E / On Behalf Of The GeoMx Breast Cancer Consortium

Cancers

2021 Volume 13, Issue 17

Abstract: Breast cancer is a heterogenous disease with variability in tumor cells and in the surrounding tumor microenvironment (TME). Understanding the molecular diversity in breast cancer is critical for improving prediction of therapeutic response and ... ...

Abstract	Breast cancer is a heterogenous disease with variability in tumor cells and in the surrounding tumor microenvironment (TME). Understanding the molecular diversity in breast cancer is critical for improving prediction of therapeutic response and prognostication. High-plex spatial profiling of tumors enables characterization of heterogeneity in the breast TME, which can holistically illuminate the biology of tumor growth, dissemination and, ultimately, response to therapy. The GeoMx Digital Spatial Profiler (DSP) enables researchers to spatially resolve and quantify proteins and RNA transcripts from tissue sections. The platform is compatible with both formalin-fixed paraffin-embedded and frozen tissues. RNA profiling was developed at the whole transcriptome level for human and mouse samples and protein profiling of 100-plex for human samples. Tissue can be optically segmented for analysis of regions of interest or cell populations to study biology-directed tissue characterization. The GeoMx Breast Cancer Consortium (GBCC) is composed of breast cancer researchers who are developing innovative approaches for spatial profiling to accelerate biomarker discovery. Here, the GBCC presents best practices for GeoMx profiling to promote the collection of high-quality data, optimization of data analysis and integration of datasets to advance collaboration and meta-analyses. Although the capabilities of the platform are presented in the context of breast cancer research, they can be generalized to a variety of other tumor types that are characterized by high heterogeneity.
Language	English
Publishing date	2021-09-04
Publishing country	Switzerland
Document type	Guideline
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13174456
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Article ; Online: The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer.

Freed-Pastor, William A / Lambert, Laurens J / Ely, Zackery A / Pattada, Nimisha B / Bhutkar, Arjun / Eng, George / Mercer, Kim L / Garcia, Ana P / Lin, Lin / Rideout, William M / Hwang, William L / Schenkel, Jason M / Jaeger, Alex M / Bronson, Roderick T / Westcott, Peter M K / Hether, Tyler D / Divakar, Prajan / Reeves, Jason W / Deshpande, Vikram /

Delorey, Toni / Phillips, Devan / Yilmaz, Omer H / Regev, Aviv / Jacks, Tyler

Cancer cell

2021 Volume 39, Issue 10, Page(s) 1342–1360.e14

Abstract: The CD155/TIGIT axis can be co-opted during immune evasion in chronic viral infections and cancer. Pancreatic adenocarcinoma (PDAC) is a highly lethal malignancy, and immune-based strategies to combat this disease have been largely unsuccessful to date. ... ...

Abstract	The CD155/TIGIT axis can be co-opted during immune evasion in chronic viral infections and cancer. Pancreatic adenocarcinoma (PDAC) is a highly lethal malignancy, and immune-based strategies to combat this disease have been largely unsuccessful to date. We corroborate prior reports that a substantial portion of PDAC harbors predicted high-affinity MHC class I-restricted neoepitopes and extend these findings to advanced/metastatic disease. Using multiple preclinical models of neoantigen-expressing PDAC, we demonstrate that intratumoral neoantigen-specific CD8
MeSH term(s)	Animals ; Humans ; Immune Evasion/immunology ; Immunotherapy/methods ; Lymphocytes, Tumor-Infiltrating/metabolism ; Mice ; Pancreatic Neoplasms/immunology ; Receptors, Virus/immunology ; Pancreatic Neoplasms
Chemical Substances	Receptors, Virus ; poliovirus receptor
Language	English
Publishing date	2021-08-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2021.07.007
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Article ; Online: Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb.

Khan, Mona / Yoo, Seung-Jun / Clijsters, Marnick / Backaert, Wout / Vanstapel, Arno / Speleman, Kato / Lietaer, Charlotte / Choi, Sumin / Hether, Tyler D / Marcelis, Lukas / Nam, Andrew / Pan, Liuliu / Reeves, Jason W / Van Bulck, Pauline / Zhou, Hai / Bourgeois, Marc / Debaveye, Yves / De Munter, Paul / Gunst, Jan /

Jorissen, Mark / Lagrou, Katrien / Lorent, Natalie / Neyrinck, Arne / Peetermans, Marijke / Thal, Dietmar Rudolf / Vandenbriele, Christophe / Wauters, Joost / Mombaerts, Peter / Van Gerven, Laura

Cell

2021 Volume 184, Issue 24, Page(s) 5932–5949.e15

Abstract	Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.
MeSH term(s)	Aged ; Anosmia ; Autopsy/methods ; COVID-19/mortality ; COVID-19/physiopathology ; COVID-19/virology ; Endoscopy/methods ; Female ; Glucuronosyltransferase/biosynthesis ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Microscopy, Fluorescence ; Middle Aged ; Olfaction Disorders ; Olfactory Bulb/virology ; Olfactory Mucosa/virology ; Olfactory Receptor Neurons/metabolism ; Respiratory Mucosa/virology ; Respiratory System ; SARS-CoV-2 ; Smell
Chemical Substances	Glucuronosyltransferase (EC 2.4.1.17) ; UGT2A1 protein, human (EC 2.4.1.17)
Language	English
Publishing date	2021-11-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.10.027
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Article: The effects of mismatch repair and RAD1 genes on interchromosomal crossover recombination in Saccharomyces cerevisiae.

Nicholson, Ainsley / Fabbri, Rebecca M / Reeves, Jason W / Crouse, Gray F

Genetics

2006 Volume 173, Issue 2, Page(s) 647–659

Abstract: We have previously shown that recombination between 400-bp substrates containing only 4-bp differences, when present in an inverted repeat orientation, is suppressed by >20-fold in wild-type strains of S. cerevisiae. Among the genes involved in this ... ...

Abstract	We have previously shown that recombination between 400-bp substrates containing only 4-bp differences, when present in an inverted repeat orientation, is suppressed by >20-fold in wild-type strains of S. cerevisiae. Among the genes involved in this suppression were three genes involved in mismatch repair--MSH2, MSH3, and MSH6--and one in nucleotide excision repair, RAD1. We now report the involvement of these genes in interchromosomal recombination occurring via crossovers using these same short substrates. In these experiments, recombination was stimulated by a double-strand break generated by the HO endonuclease and can occur between completely identical (homologous) substrates or between nonidentical (homeologous) substrates. In addition, a unique feature of this system is that recombining DNA strands can be given a choice of either type of substrate. We find that interchromosomal crossover recombination with these short substrates is severely inhibited in the absence of MSH2, MSH3, or RAD1 and is relatively insensitive to the presence of mismatches. We propose that crossover recombination with these short substrates requires the products of MSH2, MSH3, and RAD1 and that these proteins have functions in recombination in addition to the removal of terminal nonhomology. We further propose that the observed insensitivity to homeology is a result of the difference in recombinational mechanism and/or the timing of the observed recombination events. These results are in contrast with those obtained using longer substrates and may be particularly relevant to recombination events between the abundant short repeated sequences that characterize the genomes of higher eukaryotes.
MeSH term(s)	Base Pair Mismatch ; Base Sequence ; Chromosomes, Fungal/genetics ; Crossing Over, Genetic ; DNA Repair/genetics ; DNA Repair Enzymes ; DNA, Fungal/chemistry ; DNA, Fungal/genetics ; DNA, Fungal/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Deoxyribonucleases, Type II Site-Specific/genetics ; Deoxyribonucleases, Type II Site-Specific/metabolism ; Endonucleases/genetics ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Genes, Fungal ; Introns ; Models, Genetic ; MutS Homolog 2 Protein/genetics ; MutS Homolog 2 Protein/metabolism ; MutS Homolog 3 Protein ; Recombination, Genetic ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Substrate Specificity
Chemical Substances	DNA, Fungal ; DNA-Binding Proteins ; Fungal Proteins ; MSH3 protein, S cerevisiae ; MutS Homolog 3 Protein ; Saccharomyces cerevisiae Proteins ; Endonucleases (EC 3.1.-) ; RAD1 protein, S cerevisiae (EC 3.1.-) ; HO protein, S cerevisiae (EC 3.1.21.-) ; SCEI protein, S cerevisiae (EC 3.1.21.-) ; Deoxyribonucleases, Type II Site-Specific (EC 3.1.21.4) ; MSH2 protein, S cerevisiae (EC 3.6.1.3) ; MutS Homolog 2 Protein (EC 3.6.1.3) ; DNA Repair Enzymes (EC 6.5.1.-)
Language	English
Publishing date	2006-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2167-2
ISSN	1943-2631 ; 0016-6731
ISSN (online)	1943-2631
ISSN	0016-6731
DOI	10.1534/genetics.105.055244
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Article: Oligonucleotide transformation of yeast reveals mismatch repair complexes to be differentially active on DNA replication strands

Kow, Yoke W / Bao, Gaobin / Reeves, Jason W / Jinks-Robertson, Sue / Crouse, Gray F

Proceedings of the National Academy of Sciences of the United States of America. 2007 July 3, v. 104, no. 27

2007

Abstract: Transformation of both prokaryotes and eukaryotes with single-stranded oligonucleotides can transfer sequence information from the oligonucleotide to the chromosome. We have studied this process using oligonucleotides that correct a -1 frameshift ... ...

Abstract	Transformation of both prokaryotes and eukaryotes with single-stranded oligonucleotides can transfer sequence information from the oligonucleotide to the chromosome. We have studied this process using oligonucleotides that correct a -1 frameshift mutation in the LYS2 gene of Saccharomyces cerevisiae. We demonstrate that transformation by oligonucleotides occurs preferentially on the lagging strand of replication and is strongly inhibited by the mismatch-repair system. These results are consistent with a mechanism in which oligonucleotides anneal to single-stranded regions of DNA at a replication fork and serve as primers for DNA synthesis. Because the mispairs the primers create are efficiently removed by the mismatch-repair system, single-stranded oligonucleotides can be used to probe mismatch-repair function in a chromosomal context. Removal of mispairs created by annealing of the single-stranded oligonucleotides to the chromosomal DNA is as expected, with 7-nt loops being recognized solely by MutSβ and 1-nt loops being recognized by both MutSα and MutSβ. We also find evidence for Mlh1-independent repair of 7-nt, but not 1-nt, loops. Unexpectedly, we find a strand asymmetry of mismatch-repair function; transformation is blocked more efficiently by MutSα on the lagging strand of replication, whereas MutSβ does not show a significant strand bias. These results suggest an inherent strand-related difference in how the yeast MutSα and MutSβ complexes access and/or repair mismatches that arise in the context of DNA replication.
Keywords	Saccharomyces cerevisiae ; yeasts ; base pair mismatch ; DNA repair ; genetic transformation ; oligonucleotides ; genes ; DNA replication ; DNA-binding proteins
Language	English
Dates of publication	2007-0703
Size	p. 11352-11357.
Publishing place	National Academy of Sciences
Document type	Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
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