Suppression of duplication-mediated gross chromosomal rearrangements (GCRs) is essential to maintain genome integrity in eukaryotes. Here we report that SUMO ligase Mms21 has a strong role in suppressing GCRs in Saccharomyces cerevisiae, while Siz1 and Siz2 have weaker and partially redundant roles. Understanding the functions of these enzymes has been hampered by a paucity of knowledge of their substrate specificity in vivo. Using a new quantitative SUMO-proteomics technology, we found that Siz1 and Siz2 redundantly control the abundances of most sumoylated substrates, while Mms21 more specifically regulates sumoylation of RNA polymerase-I and the SMC-family proteins. Interestingly, Esc2, a SUMO-like domain-containing protein, specifically promotes the accumulation of sumoylated Mms21-specific substrates and functions with Mms21 to suppress GCRs. On the other hand, the Slx5-Slx8 complex, a SUMO-targeted ubiquitin ligase, suppresses the accumulation of sumoylated Mms21-specific substrates. Thus, distinct SUMO ligases work in concert with Esc2 and Slx5-Slx8 to control substrate specificity and sumoylation homeostasis to prevent GCRs.
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http://dx.doi.org/10.1371/journal.pgen.1003670 | DOI Listing |
Front Cell Neurosci
December 2024
Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Introduction: Abnormal intracellular accumulation of Tau aggregates is a hallmark of Alzheimer's disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD). Tau deposits primarily affect neurons, but evidence indicates that glial cells may also be affected and contribute distinctively to disease progression. Cells can respond to toxic insults by orchestrating global changes in posttranslational modifications of their proteome.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2024
Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russian Federation; Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, 141980, Russian Federation. Electronic address:
One of the promising drug delivery tools is ferritin, which features high stability at a wide range of conditions and protects cargo by its spherical protein shell. We studied the self-assembly into homoglobules of ferritin from H. pylori and a chimeric protein ferritin-SUMO.
View Article and Find Full Text PDFJ Transl Med
December 2024
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010, Málaga, Spain.
Background: The gut microbiome has been reported to induce epigenetic modifications in the host, which may be involved in the pathophysiology of metabolic diseases.
Objective: To evaluate the potential interactions between the gut microbiome and DNA methylome in subjects with different metabolic characteristics.
Methods: Sixty-four participants with different metabolic characteristics (i.
Int J Biol Sci
November 2024
Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, China.
Glioblastoma multiforme (GBM) is a highly heterogeneous brain tumor with limited treatment options. Recent studies revealed cellular heterogeneity and the potential for interconversion between distinct cell types on the basis of RNA sequencing and single-cell analyses. The ability of different cell types to adapt to their surrounding environment and undergo transformation significantly complicates the study and treatment of GBM.
View Article and Find Full Text PDFACS Chem Biol
November 2024
National Institute of Biological Sciences, Beijing 102206, China.
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