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  1. Article ; Online: CDK activity at the centrosome regulates the cell cycle.

    Roberts, Emma L / Greenwood, Jessica / Kapadia, Nitin / Auchynnikava, Tania / Basu, Souradeep / Nurse, Paul

    Cell reports

    2024  Volume 43, Issue 4, Page(s) 114066

    Abstract: In human cells and yeast, an intact "hydrophobic patch" substrate docking site is needed for mitotic cyclin centrosomal localization. A hydrophobic patch mutant (HPM) of the fission yeast mitotic cyclin Cdc13 cannot enter mitosis, but whether this is due ...

    Abstract In human cells and yeast, an intact "hydrophobic patch" substrate docking site is needed for mitotic cyclin centrosomal localization. A hydrophobic patch mutant (HPM) of the fission yeast mitotic cyclin Cdc13 cannot enter mitosis, but whether this is due to defective centrosomal localization or defective cyclin-substrate docking more widely is unknown. Here, we show that artificially restoring Cdc13-HPM centrosomal localization promotes mitotic entry and increases CDK (cyclin-dependent kinase) substrate phosphorylation at the centrosome and in the cytoplasm. We also show that the S-phase B-cyclin hydrophobic patch is required for centrosomal localization but not for S phase. We propose that the hydrophobic patch is essential for mitosis due to its requirement for the local concentration of cyclin-CDK with CDK substrates and regulators at the centrosome. Our findings emphasize the central importance of the centrosome as a hub coordinating cell-cycle control and explain why the cyclin hydrophobic patch is essential for mitosis.
    MeSH term(s) Centrosome/metabolism ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/metabolism ; Cyclin-Dependent Kinases/metabolism ; Cell Cycle ; Mitosis ; Phosphorylation ; Cell Cycle Proteins/metabolism ; Cell Cycle Proteins/genetics ; Hydrophobic and Hydrophilic Interactions ; Humans ; Cyclin B
    Chemical Substances Schizosaccharomyces pombe Proteins ; Cyclin-Dependent Kinases (EC 2.7.11.22) ; Cdc13 protein, S pombe ; Cell Cycle Proteins ; Cyclin B
    Language English
    Publishing date 2024-04-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2024.114066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Core control principles of the eukaryotic cell cycle.

    Basu, Souradeep / Greenwood, Jessica / Jones, Andrew W / Nurse, Paul

    Nature

    2022  Volume 607, Issue 7918, Page(s) 381–386

    Abstract: Cyclin-dependent kinases (CDKs) lie at the heart of eukaryotic cell cycle control, with different cyclin-CDK complexes initiating DNA replication (S-CDKs) and mitosis (M-CDKs) ...

    Abstract Cyclin-dependent kinases (CDKs) lie at the heart of eukaryotic cell cycle control, with different cyclin-CDK complexes initiating DNA replication (S-CDKs) and mitosis (M-CDKs)
    MeSH term(s) Cell Cycle ; Centrosome ; Cyclin-Dependent Kinases/metabolism ; Cyclins/metabolism ; Eukaryotic Cells/cytology ; Eukaryotic Cells/enzymology ; Eukaryotic Cells/metabolism ; Mitosis ; Models, Biological ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Phosphatase 1 ; Proteomics ; S Phase ; Schizosaccharomyces/cytology ; Schizosaccharomyces/enzymology ; Schizosaccharomyces/metabolism ; Substrate Specificity
    Chemical Substances Cyclins ; Phosphoproteins ; Cyclin-Dependent Kinases (EC 2.7.11.22) ; Protein Phosphatase 1 (EC 3.1.3.16)
    Language English
    Publishing date 2022-06-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-022-04798-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A CDK activity buffer ensures mitotic completion.

    Basu, Souradeep / Patterson, James O / Zeisner, Theresa U / Nurse, Paul

    Journal of cell science

    2022  Volume 135, Issue 12

    Abstract: The eukaryotic cell cycle is driven by the activity of cyclin-dependent kinases (CDKs). CDK activity rises over 50-fold during the cell cycle, from a low level in G1 to a high level in mitosis. However, it is not known whether the entire range of CDK ... ...

    Abstract The eukaryotic cell cycle is driven by the activity of cyclin-dependent kinases (CDKs). CDK activity rises over 50-fold during the cell cycle, from a low level in G1 to a high level in mitosis. However, it is not known whether the entire range of CDK activity is necessary for cell cycle progression, or whether cells can tolerate a reduction in CDK activity level. Here, in fission yeast, we show that sublethal CDK inhibition lengthens the time cells spend in mitosis but does not cause misordering of mitotic events. Maximum attainable CDK activity exceeds the amount necessary for mitosis, and thus forms a CDK activity buffer between sufficient and maximal possible CDK activities. This CDK activity buffer is needed for mitotic completion when CDK activity is compromised, and CDK inhibition only becomes lethal to cells when this buffer is exhausted. Finally, we explore what factors influence this CDK activity buffer, and find that it is influenced by CDK-counteracting phosphatases. Therefore, maximum attainable CDK activity is not necessary for mitosis but provides robustness to CDK activity reduction to ensure mitotic completion.
    MeSH term(s) Cell Cycle Proteins/metabolism ; Cyclin-Dependent Kinases/genetics ; Cyclin-Dependent Kinases/metabolism ; Mitosis ; Phosphorylation ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism
    Chemical Substances Cell Cycle Proteins ; Schizosaccharomyces pombe Proteins ; Cyclin-Dependent Kinases (EC 2.7.11.22)
    Language English
    Publishing date 2022-06-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.259626
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Imide arylation with aryl(TMP)iodonium tosylates.

    Basu, Souradeep / Sandtorv, Alexander H / Stuart, David R

    Beilstein journal of organic chemistry

    2018  Volume 14, Page(s) 1034–1038

    Abstract: Herein, we describe the synthesis ... ...

    Abstract Herein, we describe the synthesis of
    Language English
    Publishing date 2018-05-11
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2192461-2
    ISSN 1860-5397
    ISSN 1860-5397
    DOI 10.3762/bjoc.14.90
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: CDK control pathways integrate cell size and ploidy information to control cell division

    James Oliver Patterson / Souradeep Basu / Paul Rees / Paul Nurse

    eLife, Vol

    2021  Volume 10

    Abstract: Maintenance of cell size homeostasis is a property that is conserved throughout eukaryotes. Cell size homeostasis is brought about by the co-ordination of cell division with cell growth and requires restriction of smaller cells from undergoing mitosis ... ...

    Abstract Maintenance of cell size homeostasis is a property that is conserved throughout eukaryotes. Cell size homeostasis is brought about by the co-ordination of cell division with cell growth and requires restriction of smaller cells from undergoing mitosis and cell division, whilst allowing larger cells to do so. Cyclin-CDK is the fundamental driver of mitosis and therefore ultimately ensures size homeostasis. Here we dissect determinants of CDK activity in vivo to investigate how cell size information is processed by the cell cycle network in fission yeast. We develop a high-throughput single-cell assay system of CDK activity in vivo and show that inhibitory tyrosine phosphorylation of CDK encodes cell size information, with the phosphatase PP2A aiding to set a size threshold for division. CDK inhibitory phosphorylation works synergistically with PP2A to prevent mitosis in smaller cells. Finally, we find that diploid cells of equivalent size to haploid cells exhibit lower CDK activity in response to equal cyclin-CDK enzyme concentrations, suggesting that CDK activity is reduced by increased DNA levels. Therefore, scaling of cyclin-CDK levels with cell size, CDK inhibitory phosphorylation, PP2A, and DNA-dependent inhibition of CDK activity, all inform the cell cycle network of cell size, thus contributing to cell size homeostasis.
    Keywords cell cycle ; synthetic biology ; cell size control ; CDK ; cyclin ; PP2A ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: CDK control pathways integrate cell size and ploidy information to control cell division.

    Patterson, James Oliver / Basu, Souradeep / Rees, Paul / Nurse, Paul

    eLife

    2021  Volume 10

    Abstract: Maintenance of cell size homeostasis is a property that is conserved throughout eukaryotes. Cell size homeostasis is brought about by the co-ordination of cell division with cell growth and requires restriction of smaller cells from undergoing mitosis ... ...

    Abstract Maintenance of cell size homeostasis is a property that is conserved throughout eukaryotes. Cell size homeostasis is brought about by the co-ordination of cell division with cell growth and requires restriction of smaller cells from undergoing mitosis and cell division, whilst allowing larger cells to do so. Cyclin-CDK is the fundamental driver of mitosis and therefore ultimately ensures size homeostasis. Here we dissect determinants of CDK activity in vivo to investigate how cell size information is processed by the cell cycle network in fission yeast. We develop a high-throughput single-cell assay system of CDK activity in vivo and show that inhibitory tyrosine phosphorylation of CDK encodes cell size information, with the phosphatase PP2A aiding to set a size threshold for division. CDK inhibitory phosphorylation works synergistically with PP2A to prevent mitosis in smaller cells. Finally, we find that diploid cells of equivalent size to haploid cells exhibit lower CDK activity in response to equal cyclin-CDK enzyme concentrations, suggesting that CDK activity is reduced by increased DNA levels. Therefore, scaling of cyclin-CDK levels with cell size, CDK inhibitory phosphorylation, PP2A, and DNA-dependent inhibition of CDK activity, all inform the cell cycle network of cell size, thus contributing to cell size homeostasis.
    MeSH term(s) Cell Cycle ; Cell Division ; Cell Size ; Cyclin-Dependent Kinases/genetics ; Cyclin-Dependent Kinases/metabolism ; Cyclins/genetics ; Cyclins/metabolism ; Homeostasis ; Mitosis ; Phosphorylation ; Ploidies ; Protein Phosphatase 2/metabolism ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism
    Chemical Substances Cyclins ; Schizosaccharomyces pombe Proteins ; Cyclin-Dependent Kinases (EC 2.7.11.22) ; Protein Phosphatase 2 (EC 3.1.3.16)
    Language English
    Publishing date 2021-06-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.64592
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Imide arylation with aryl(TMP)iodonium tosylates

    Souradeep Basu / Alexander H. Sandtorv / David R. Stuart

    Beilstein Journal of Organic Chemistry, Vol 14, Iss 1, Pp 1034-

    2018  Volume 1038

    Abstract: Herein, we describe the synthesis of N-aryl phthalimides by metal-free coupling of potassium phthalimide with unsymmetrical aryl(TMP)iodonium tosylate salts. The aryl transfer from the iodonium moiety occurs under electronic control with the electron- ... ...

    Abstract Herein, we describe the synthesis of N-aryl phthalimides by metal-free coupling of potassium phthalimide with unsymmetrical aryl(TMP)iodonium tosylate salts. The aryl transfer from the iodonium moiety occurs under electronic control with the electron-rich trimethoxyphenyl group acting as a competent dummy ligand. The yields of N-aryl phthalimides are moderate to high and the coupling reaction is compatible with electron-deficient and sterically encumbered aryl groups.
    Keywords arylation ; C–N coupling ; diaryliodonium ; hypercoordinate iodine ; metal-free ; Science ; Q ; Organic chemistry ; QD241-441
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Beilstein-Institut
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Upper respiratory tract microbiome profiles in SARS-CoV-2 Delta and Omicron infected patients exhibit variant specific patterns and robust prediction of disease groups.

    Nath, Shankha / Sarkar, Mousumi / Maddheshiya, Ankita / De, Debjit / Paul, Shouvik / Dey, Souradeep / Pal, Kuhu / Roy, Suman Kr / Ghosh, Ayan / Sengupta, Sharmila / Paine, Suman Kalyan / Biswas, Nidhan K / Basu, Analabha / Mukherjee, Souvik

    Microbiology spectrum

    2023  Volume 11, Issue 6, Page(s) e0236823

    Abstract: Importance: The role of the upper respiratory tract (URT) microbiome in predicting lung health has been documented in several studies. The dysbiosis in COVID patients has been associated with disease outcomes by modulating the host immune system. ... ...

    Abstract Importance: The role of the upper respiratory tract (URT) microbiome in predicting lung health has been documented in several studies. The dysbiosis in COVID patients has been associated with disease outcomes by modulating the host immune system. However, although it has been known that different SARS-CoV-2 variants manifest distinct transmissibility and mortality rates in human populations, their effect on the composition and diversity of the URT microbiome has not been studied to date. Unlike the older variant (Delta), the newer variant (Omicron) have become more transmissible with lesser mortality and the symptoms have also changed significantly. Hence, in the present study, we have investigated the change in the URT microbiome associated with Delta and Omicron variants and identified variant-specific signatures that will be useful in the assessment of lung health and can be utilized for nasal probiotic therapy in the future.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; COVID-19 ; Microbiota/genetics ; Nose
    Language English
    Publishing date 2023-10-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.02368-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The Hydrophobic Patch Directs Cyclin B to Centrosomes to Promote Global CDK Phosphorylation at Mitosis.

    Basu, Souradeep / Roberts, Emma L / Jones, Andrew W / Swaffer, Matthew P / Snijders, Ambrosius P / Nurse, Paul

    Current biology : CB

    2020  Volume 30, Issue 5, Page(s) 883–892.e4

    Abstract: The cyclin-dependent kinases (CDKs) are the major cell-cycle regulators that phosphorylate hundreds of substrates, controlling the onset of S phase and M phase [1-3]. However, the patterns of substrate phosphorylation increase are not uniform, as ... ...

    Abstract The cyclin-dependent kinases (CDKs) are the major cell-cycle regulators that phosphorylate hundreds of substrates, controlling the onset of S phase and M phase [1-3]. However, the patterns of substrate phosphorylation increase are not uniform, as different substrates become phosphorylated at different times as cells proceed through the cell cycle [4, 5]. In fission yeast, the correct ordering of CDK substrate phosphorylation can be established by the activity of a single mitotic cyclin-CDK complex [6, 7]. Here, we investigate the substrate-docking region, the hydrophobic patch, on the fission yeast mitotic cyclin Cdc13 as a potential mechanism to correctly order CDK substrate phosphorylation. We show that the hydrophobic patch targets Cdc13 to the yeast centrosome equivalent, the spindle pole body (SPB), and disruption of this motif prevents both centrosomal localization of Cdc13 and the onset of mitosis but does not prevent S phase. CDK phosphorylation in mitosis is compromised for approximately half of all mitotic CDK substrates, with substrates affected generally being those that require the highest levels of CDK activity to become phosphorylated and those that are located at the SPB. Our experiments suggest that the hydrophobic patch of mitotic cyclins contributes to CDK substrate selection by directing the localization of Cdc13-CDK to centrosomes and that this localization of CDK contributes to the CDK substrate phosphorylation necessary to ensure proper entry into mitosis. Finally, we show that mutation of the hydrophobic patch prevents cyclin B1 localization to centrosomes in human cells, suggesting that this mechanism of cyclin-CDK spatial regulation may be conserved across eukaryotes.
    MeSH term(s) Cell Line ; Centrosome/metabolism ; Cyclin B1/metabolism ; Cyclin-Dependent Kinases/metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Phosphorylation ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/metabolism
    Chemical Substances CCNB1 protein, human ; Cyclin B1 ; Schizosaccharomyces pombe Proteins ; Cyclin-Dependent Kinases (EC 2.7.11.22)
    Language English
    Publishing date 2020-02-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2019.12.053
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Synthesis of Crescent Shaped Heterocycle-fused Aromatics via Garratt-Braverman Cyclization and Their DNA-binding Studies

    Ghosh, Debaki / Souradeep Basu / Monisha Singha / Joyee Das / Prabuddha Bhattacharya / Amit Basak

    Tetrahedron letters. 2017,

    2017  

    Abstract: Three crescent shaped heterocycle-fused phenanthrene based systems 1-3 have been synthesized starting from benzene (or substituted benzene) 1,2-bis-propargyl alcohols. Bis-alkylation with propargylic bromides provided the key intermediate, the bis- ... ...

    Abstract Three crescent shaped heterocycle-fused phenanthrene based systems 1-3 have been synthesized starting from benzene (or substituted benzene) 1,2-bis-propargyl alcohols. Bis-alkylation with propargylic bromides provided the key intermediate, the bis-propargyl bis-ethers. In spite of the possibility of many competing reactions, the latter underwent facile double Garratt-Braverman Cyclization to provide compounds 1-3 in near quantitative yield, in a striking reaction involving the formation of four C-C bonds in a single step. Compounds 1-3 showed binding interaction with DNA, predominantly, via groove binding along with partial intercalation (combilexins). Molecular docking study supported the propsed binding modes.
    Keywords DNA ; alcohols ; benzene ; bromides ; chemical bonding ; chemical reactions ; chemical structure ; molecular models ; phenanthrene
    Language English
    Size p. .
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 204287-3
    ISSN 1873-3581 ; 0040-4039
    ISSN (online) 1873-3581
    ISSN 0040-4039
    DOI 10.1016/j.tetlet.2017.04.003
    Database NAL-Catalogue (AGRICOLA)

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