Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation
Biochem J. 2024 Jun 5;481(11):683-715. doi: 10.1042/BCJ20230262.ABSTRACTHuman mitochondria possess a multi-copy circular genome, mitochondrial DNA (mtDNA), that is essential for cellular energy metabolism. The number of copies of mtDNA per cell, and their integrity, are maintained by nuclear-encoded mtDNA replication and repair machineries. Aberrant mtDNA replication and mtDNA breakage are believed to cause deletions within mtDNA. The genomic location and breakpoint sequences of these deletions show similar patterns across various inherited and acquired diseases, and are also observed during normal ageing, suggesting a com...
Source: The Biochemical Journal - May 28, 2024 Category: Biochemistry Authors: Tiago M Bernardino Gomes Amy E Vincent Katja E Menger James B Stewart Thomas J Nicholls Source Type: research
Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation
Biochem J. 2024 Jun 5;481(11):683-715. doi: 10.1042/BCJ20230262.ABSTRACTHuman mitochondria possess a multi-copy circular genome, mitochondrial DNA (mtDNA), that is essential for cellular energy metabolism. The number of copies of mtDNA per cell, and their integrity, are maintained by nuclear-encoded mtDNA replication and repair machineries. Aberrant mtDNA replication and mtDNA breakage are believed to cause deletions within mtDNA. The genomic location and breakpoint sequences of these deletions show similar patterns across various inherited and acquired diseases, and are also observed during normal ageing, suggesting a com...
Source: The Biochemical Journal - May 28, 2024 Category: Biochemistry Authors: Tiago M Bernardino Gomes Amy E Vincent Katja E Menger James B Stewart Thomas J Nicholls Source Type: research
RNA processing by the CRISPR-associated NYN ribonuclease
This study sheds light on the functional relevance of CRISPR-associated NYN proteins and highlights the complexity of CRISPR-mediated defence strategies in bacteria.PMID:38785320 | DOI:10.1042/BCJ20240151 (Source: The Biochemical Journal)
Source: The Biochemical Journal - May 24, 2024 Category: Biochemistry Authors: Haotian Chi Malcolm F White Source Type: research
RNA processing by the CRISPR-associated NYN ribonuclease
This study sheds light on the functional relevance of CRISPR-associated NYN proteins and highlights the complexity of CRISPR-mediated defence strategies in bacteria.PMID:38785320 | DOI:10.1042/BCJ20240151 (Source: The Biochemical Journal)
Source: The Biochemical Journal - May 24, 2024 Category: Biochemistry Authors: Haotian Chi Malcolm F White Source Type: research
RNA processing by the CRISPR-associated NYN ribonuclease
This study sheds light on the functional relevance of CRISPR-associated NYN proteins and highlights the complexity of CRISPR-mediated defence strategies in bacteria.PMID:38785320 | DOI:10.1042/BCJ20240151 (Source: The Biochemical Journal)
Source: The Biochemical Journal - May 24, 2024 Category: Biochemistry Authors: Haotian Chi Malcolm F White Source Type: research
RNA processing by the CRISPR-associated NYN ribonuclease
This study sheds light on the functional relevance of CRISPR-associated NYN proteins and highlights the complexity of CRISPR-mediated defence strategies in bacteria.PMID:38785320 | DOI:10.1042/BCJ20240151 (Source: The Biochemical Journal)
Source: The Biochemical Journal - May 24, 2024 Category: Biochemistry Authors: Haotian Chi Malcolm F White Source Type: research
Sulfoquinovosyl diacylglycerol is required for dimerization of the Rhodobacter sphaeroides RC-LH1 core complex
Biochem J. 2024 May 23:BCJ20240125. doi: 10.1042/BCJ20240125. Online ahead of print.ABSTRACTThe reaction centre-light harvesting 1 (RC-LH1) core complex is indispensable for anoxygenic photosynthesis. In the purple bacterium Rhodobacter (Rba.) sphaeroides RC-LH1 is produced both as a monomer in which 14 LH1 subunits form a C-shaped antenna around one RC, and as a dimer, where 28 LH1 subunits form an S-shaped antenna surrounding two RCs. Alongside the five RC and LH1 subunits, an additional polypeptide known as PufX provides an interface for dimerization and also prevents LH1 ring closure, introducing a channel for quinone ...
Source: The Biochemical Journal - May 23, 2024 Category: Biochemistry Authors: Elizabeth C Martin Adam Gm Bowie Taylor Wellfare Reid C Neil Hunter Andrew Hitchcock David Jk Swainsbury Source Type: research
Cancer-Associated Mutations in Protein Kinase C Theta are Loss-of-Function
Biochem J. 2024 May 16:BCJ20240148. doi: 10.1042/BCJ20240148. Online ahead of print.ABSTRACTThe Ca2+-independent, but diacylglycerol-regulated, novel protein kinase C (PKC) theta (θ) is highly expressed in hematopoietic cells where it participates in immune signaling and platelet function. Mounting evidence suggests that PKCθ may be involved in cancer, particularly blood cancers, breast cancer, and gastrointestinal stromal tumors (GISTs), yet how to target this kinase (as an oncogene or as a tumor suppressor) has not been established. Here, we examine the effect of four cancer-associated mutations, R145H/C in the autoinh...
Source: The Biochemical Journal - May 16, 2024 Category: Biochemistry Authors: Stefanie Jill Hodapp Nathan Gravel Natarajan Kannan Alexandra C Newton Source Type: research
The monodomain Kunitz protein EgKU-7 from Echinococcus granulosus, the dog tapeworm, is a high-affinity trypsin inhibitor with two interaction sites
Biochem J. 2024 May 16:BCJ20230514. doi: 10.1042/BCJ20230514. Online ahead of print.ABSTRACTTypical Kunitz proteins (I2 family of the MEROPS database, Kunitz-A family) are metazoan competitive inhibitors of serine peptidases that form tight complexes of 1:1 stoichiometry, mimicking substrates. The cestode Echinococcus granulosus, the dog tapeworm causing cystic echinococcosis in humans and livestock, encodes an expanded family of monodomain Kunitz proteins, some of which are secreted to the dog host interface. The Kunitz protein EgKU-7 contains, in addition to the Kunitz domain with the anti-peptidase loop comprising a cri...
Source: The Biochemical Journal - May 16, 2024 Category: Biochemistry Authors: Mart ín Fló Díaz Leonardo Pellizza Rosario Duran Beatriz Alvarez Cecilia Fern ández Source Type: research
Genetically engineered human embryonic kidney cells as a novel vehicle for dual patch clamp study of human gap junction channels
Biochem J. 2024 May 16:BCJ20240016. doi: 10.1042/BCJ20240016. Online ahead of print.ABSTRACTMutations in more than half of human connexin genes encoding gap junction subunits have been linked to inherited human diseases. Functional studies of human gap junction (GJ) channels are essential for revealing mechanistic insights on the etiology of disease-linked connexin mutants. However, the commonly used Xenopus oocytes, N2A, HeLa, and other model cells for recombinant expression of human connexins have different and significant limitations. Here we developed a human cell line (HEK293) with each of the endogenous connexins (Cx...
Source: The Biochemical Journal - May 16, 2024 Category: Biochemistry Authors: Honghong Chen Yi X Li Robert S Wong Jessica L Esseltine Donglin Bai Source Type: research
Cancer-Associated Mutations in Protein Kinase C Theta are Loss-of-Function
Biochem J. 2024 May 16:BCJ20240148. doi: 10.1042/BCJ20240148. Online ahead of print.ABSTRACTThe Ca2+-independent, but diacylglycerol-regulated, novel protein kinase C (PKC) theta (θ) is highly expressed in hematopoietic cells where it participates in immune signaling and platelet function. Mounting evidence suggests that PKCθ may be involved in cancer, particularly blood cancers, breast cancer, and gastrointestinal stromal tumors (GISTs), yet how to target this kinase (as an oncogene or as a tumor suppressor) has not been established. Here, we examine the effect of four cancer-associated mutations, R145H/C in the autoinh...
Source: The Biochemical Journal - May 16, 2024 Category: Biochemistry Authors: Stefanie Jill Hodapp Nathan Gravel Natarajan Kannan Alexandra C Newton Source Type: research
The monodomain Kunitz protein EgKU-7 from Echinococcus granulosus, the dog tapeworm, is a high-affinity trypsin inhibitor with two interaction sites
Biochem J. 2024 May 16:BCJ20230514. doi: 10.1042/BCJ20230514. Online ahead of print.ABSTRACTTypical Kunitz proteins (I2 family of the MEROPS database, Kunitz-A family) are metazoan competitive inhibitors of serine peptidases that form tight complexes of 1:1 stoichiometry, mimicking substrates. The cestode Echinococcus granulosus, the dog tapeworm causing cystic echinococcosis in humans and livestock, encodes an expanded family of monodomain Kunitz proteins, some of which are secreted to the dog host interface. The Kunitz protein EgKU-7 contains, in addition to the Kunitz domain with the anti-peptidase loop comprising a cri...
Source: The Biochemical Journal - May 16, 2024 Category: Biochemistry Authors: Mart ín Fló Díaz Leonardo Pellizza Rosario Duran Beatriz Alvarez Cecilia Fern ández Source Type: research
Genetically engineered human embryonic kidney cells as a novel vehicle for dual patch clamp study of human gap junction channels
Biochem J. 2024 May 16:BCJ20240016. doi: 10.1042/BCJ20240016. Online ahead of print.ABSTRACTMutations in more than half of human connexin genes encoding gap junction subunits have been linked to inherited human diseases. Functional studies of human gap junction (GJ) channels are essential for revealing mechanistic insights on the etiology of disease-linked connexin mutants. However, the commonly used Xenopus oocytes, N2A, HeLa, and other model cells for recombinant expression of human connexins have different and significant limitations. Here we developed a human cell line (HEK293) with each of the endogenous connexins (Cx...
Source: The Biochemical Journal - May 16, 2024 Category: Biochemistry Authors: Honghong Chen Yi X Li Robert S Wong Jessica L Esseltine Donglin Bai Source Type: research
Cancer-Associated Mutations in Protein Kinase C Theta are Loss-of-Function
Biochem J. 2024 May 16:BCJ20240148. doi: 10.1042/BCJ20240148. Online ahead of print.ABSTRACTThe Ca2+-independent, but diacylglycerol-regulated, novel protein kinase C (PKC) theta (θ) is highly expressed in hematopoietic cells where it participates in immune signaling and platelet function. Mounting evidence suggests that PKCθ may be involved in cancer, particularly blood cancers, breast cancer, and gastrointestinal stromal tumors (GISTs), yet how to target this kinase (as an oncogene or as a tumor suppressor) has not been established. Here, we examine the effect of four cancer-associated mutations, R145H/C in the autoinh...
Source: The Biochemical Journal - May 16, 2024 Category: Biochemistry Authors: Stefanie Jill Hodapp Nathan Gravel Natarajan Kannan Alexandra C Newton Source Type: research
The monodomain Kunitz protein EgKU-7 from Echinococcus granulosus, the dog tapeworm, is a high-affinity trypsin inhibitor with two interaction sites
Biochem J. 2024 May 16:BCJ20230514. doi: 10.1042/BCJ20230514. Online ahead of print.ABSTRACTTypical Kunitz proteins (I2 family of the MEROPS database, Kunitz-A family) are metazoan competitive inhibitors of serine peptidases that form tight complexes of 1:1 stoichiometry, mimicking substrates. The cestode Echinococcus granulosus, the dog tapeworm causing cystic echinococcosis in humans and livestock, encodes an expanded family of monodomain Kunitz proteins, some of which are secreted to the dog host interface. The Kunitz protein EgKU-7 contains, in addition to the Kunitz domain with the anti-peptidase loop comprising a cri...
Source: The Biochemical Journal - May 16, 2024 Category: Biochemistry Authors: Mart ín Fló Díaz Leonardo Pellizza Rosario Duran Beatriz Alvarez Cecilia Fern ández Source Type: research
