Structural maintenance of chromosome (SMC) and the SMC-interacting kleisin protein families have key functions in the chromosome organization of most organisms. Here, we report that the Bacillus subtilis kleisin, ScpA, can form a ternary complex with the SMC and ScpB proteins in a yeast tri-hybrid assay, supporting the notion of a bacterial cohesin/condensin-like complex. Furthermore, ScpA interacts in two-hybrid assays with the AddAB complex, essential for recombinational repair, with DegS, a two-component sensor kinase, as well as with other potential transcription regulators. Point mutations in scpA allowing growth under conditions not permissive for the spcA null and not affecting chromosome condensation were isolated. Among these mutations, some affected DNA repair and gene regulation, thus separating ScpA functions in these two pathways from its functions in chromosome condensation and segregation. Some separation-of-function mutations in scpA caused a deficiency in the repair of mitomycin C DNA lesions that was suppressed by increasing the intracellular dosage of the interacting AddAB complex. Another mutation in scpA deregulated the expression of genes encoding degradative enzymes that are known to be controlled by the interacting DegS kinase. We propose that the SMC-ScpA-ScpB complex could: (i) recruit the AddAB helicase/nuclease to act in post-replicative repair; and (ii) form a complex with the DegS sensor kinase that inhibits its kinase activity. Moreover, our results indicate that the role of cohesin and condensin complexes in DNA repair and gene regulation is evolutionary conserved.
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http://dx.doi.org/10.1111/j.1365-2958.2003.03951.x | DOI Listing |
Physiol Plant
January 2025
Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal, Madhya Pradesh, India.
Under changing climatic conditions, plant exposure to high-intensity UV-B can be a potential threat to plant health and all plant-derived human requirements, including food. It's crucial to understand how plants respond to high UV-B radiation so that proper measures can be taken to enhance tolerance towards high UV-B stress. We found that BBX22, a B-box protein-coding gene, is strongly induced within one hour of exposure to high-intensity UV-B.
View Article and Find Full Text PDFGenome Biol Evol
January 2025
Department of Biology, University of Florence, 50019 Sesto Fiorentino, Italy.
In prokaryotes, DNA methylation plays roles in DNA repair, gene expression, cell cycle progression, and immune recognition of foreign DNA. Genome-wide methylation patterns can vary between strains, influencing phenotype, and gene transfer. However, broader evolutionary studies on bacterial epigenomic variation remain limited.
View Article and Find Full Text PDFCell Death Differ
January 2025
Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
The assembly of Tcrb and Tcra genes require double negative (DN) thymocytes to undergo multiple rounds of programmed DNA double-strand breaks (DSBs), followed by their efficient repair. However, mechanisms governing cell cycle checkpoints and specific survival pathways during the repair process remain unclear. Here, we report high-resolution scRNA-seq analyses of individually sorted mouse DN3 and DN4 thymocytes, which reveals a G2M cell cycle checkpoint, in addition to the known G1 checkpoint, during Tcrb and Tcra recombination.
View Article and Find Full Text PDFNature
January 2025
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Germline BRCA2 loss-of function variants, which can be identified through clinical genetic testing, predispose to several cancers. However, variants of uncertain significance limit the clinical utility of test results. Thus, there is a need for functional characterization and clinical classification of all BRCA2 variants to facilitate the clinical management of individuals with these variants.
View Article and Find Full Text PDFNature
January 2025
Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, CA, USA.
Breast cancer is a highly heterogeneous disease whose prognosis and treatment as defined by the expression of three receptors-oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2; encoded by ERBB2)-is insufficient to capture the full spectrum of clinical outcomes and therapeutic vulnerabilities. Previously, we demonstrated that transcriptional and genomic profiles define eleven integrative subtypes with distinct clinical outcomes, including four ER subtypes with increased risk of relapse decades after diagnosis. Here, to determine whether these subtypes reflect distinct evolutionary histories, interactions with the immune system and pathway dependencies, we established a meta-cohort of 1,828 breast tumours spanning pre-invasive, primary invasive and metastatic disease with whole-genome and transcriptome sequencing.
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