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      Deacetylation enhances ParB–DNA interactions affecting chromosome segregation in Streptomyces coelicolor

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          Abstract

          Reversible lysine acetylation plays regulatory roles in diverse biological processes, including cell metabolism, gene transcription, cell apoptosis and ageing. Here, we show that lysine acetylation is involved in the regulation of chromosome segregation, a pivotal step during cell division in Streptomyces coelicolor. Specifically, deacetylation increases the DNA-binding affinity of the chromosome segregation protein ParB to the centromere-like sequence parS. Both biochemical and genetic experiments suggest that the deacetylation process is mainly modulated by a sirtuin-like deacetylase ScCobB1. The Lys-183 residue in the helix-turn-helix region of ParB is the major deacetylation site responsible for the regulation of ParB- parS binding. In-frame deletion of SccobB1 represses formation of ParB segregation complexes and leads to generation of abnormal spores. Taken together, these observations provide direct evidence that deacetylation participates in the regulation of chromosome segregation by targeting ParB in S. coelicolor.

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          Most cited references41

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          Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

          Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.
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            Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.

            Acetylation of proteins on lysine residues is a dynamic posttranslational modification that is known to play a key role in regulating transcription and other DNA-dependent nuclear processes. However, the extent of this modification in diverse cellular proteins remains largely unknown, presenting a major bottleneck for lysine-acetylation biology. Here we report the first proteomic survey of this modification, identifying 388 acetylation sites in 195 proteins among proteins derived from HeLa cells and mouse liver mitochondria. In addition to regulators of chromatin-based cellular processes, nonnuclear localized proteins with diverse functions were identified. Most strikingly, acetyllysine was found in more than 20% of mitochondrial proteins, including many longevity regulators and metabolism enzymes. Our study reveals previously unappreciated roles for lysine acetylation in the regulation of diverse cellular pathways outside of the nucleus. The combined data sets offer a rich source for further characterization of the contribution of this modification to cellular physiology and human diseases.
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              Short- and long-term effects of chromosome mis-segregation and aneuploidy.

              Dividing cells that experience chromosome mis-segregation generate aneuploid daughter cells, which contain an incorrect number of chromosomes. Although aneuploidy interferes with the proliferation of untransformed cells, it is also, paradoxically, a hallmark of cancer, a disease defined by increased proliferative potential. These contradictory effects are also observed in mouse models of chromosome instability (CIN). CIN can inhibit and promote tumorigenesis. Recent work has provided insights into the cellular consequences of CIN and aneuploidy. Chromosome mis-segregation per se can alter the genome in many more ways than just causing the gain or loss of chromosomes. The short- and long-term effects of aneuploidy are caused by gene-specific effects and a stereotypic aneuploidy stress response. Importantly, these recent findings provide insights into the role of aneuploidy in tumorigenesis.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                21 May 2020
                20 April 2020
                20 April 2020
                : 48
                : 9
                : 4902-4914
                Affiliations
                [1 ] Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences , Chinese Academy of Sciences, Shanghai 200032, China
                [2 ] Institutes of Biomedical Sciences, Fudan University , Shanghai 200032, China
                [3 ] Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases , Shanghai 200032, China
                [4 ] Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology , Chinese Academy of Sciences, Shenzhen 518055, China
                [5 ] State Key Lab of Genetic Engineering & Institutes of Biomedical Sciences, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University , Shanghai 200433, China
                [6 ] Shanghai-MOST Key Laboratory of Disease and Health Genomics , Chinese National Human Genome Center at Shanghai, Shanghai 201203, China
                [7 ] Department of Microbiology and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong , Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China
                [8 ] College of Life Sciences, Shanghai Normal University , Shanghai 200232, China
                Author notes
                To whom correspondence should be addressed. Tel: +86 15919858900; Email: weizhao008@ 123456gmail.com
                Correspondence may also be addressed to Guo-Ping Zhao. Tel: +86 13901691631; Email: gpzhao@ 123456sibs.ac.cn
                Author information
                http://orcid.org/0000-0002-2422-8398
                Article
                gkaa245
                10.1093/nar/gkaa245
                7229854
                32313947
                874cf1e9-0fef-451e-b8d1-d5668ad9c350
                © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 03 April 2020
                : 10 March 2020
                : 11 July 2019
                Page count
                Pages: 13
                Funding
                Funded by: National Key Research and Development Program of China, DOI 10.13039/501100012166;
                Award ID: 2019YFA0904000
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 31400039
                Award ID: 31430004
                Award ID: 31421061
                Categories
                AcademicSubjects/SCI00010
                Gene regulation, Chromatin and Epigenetics

                Genetics
                Genetics

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