The bacterial chromosome: architecture and action of bacterial SMC and SMC-like complexes

Nolivos, Sophie; Sherratt, David J.

doi:10.1111/1574-6976.12045

Cited by 146 publications

(143 citation statements)

References 93 publications

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“…Indeed, bacterial GHKL ATPases, such as topoisomerase VI and gyrase, can trap DNA through dimerization of their ATPase domains. In this way, MORCs may act in a manner analogous to structural maintenance of chromosomes (SMC) proteins, such as condensins and cohesins, which use topological trapping of DNA in their mechanisms of action (24,25).…”

Section: Resultsmentioning

confidence: 99%

Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin

Yen

Pastor

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Microrchidia (MORC) proteins are GHKL (gyrase, heat-shock protein 90, histidine kinase, MutL) ATPases that function in gene regulation in multiple organisms. Animal MORCs also contain CW-type zinc finger domains, which are known to bind to modified histones. We solved the crystal structure of the murine MORC3 ATPase-CW domain bound to the nucleotide analog AMPPNP (phosphoaminophosphonic acidadenylate ester) and in complex with a trimethylated histone H3 lysine 4 (H3K4) peptide (H3K4me3). We observed that the MORC3 N-terminal ATPase domain forms a dimer when bound to AMPPNP. We used native mass spectrometry to show that dimerization is ATPdependent, and that dimer formation is enhanced in the presence of nonhydrolyzable ATP analogs. The CW domain uses an aromatic cage to bind trimethylated Lys4 and forms extensive hydrogen bonds with the H3 tail. We found that MORC3 localizes to promoters marked by H3K4me3 throughout the genome, consistent with its binding to H3K4me3 in vitro. Our work sheds light on aspects of the molecular dynamics and function of MORC3.X-ray crystallography | histone mark reader | ATPase | native mass spectrometry T he Microrchidia (MORC) family of ATPase proteins has been shown to be an important regulator of gene silencing in multiple organisms. This family was first described in mice, when it was discovered that morc1 null males showed arrested spermatogenesis (1). This arrest was later shown to be associated with transposon derepression, implicating murine MORC1 as a crucial mediator of transposon silencing (2). Arabidopsis thaliana MORC1 and MORC6 were shown to mediate silencing of transposons in a manner largely independent of changes in DNA methylation (3)(4)(5). Studies in Caenorhabditis elegans, which lack DNA methylation, also concluded that the single MORC gene in this organism plays a role in transgene silencing (4). Although the biological importance of MORC ATPases in enforcing gene silencing across multiple organisms is clear, how they are targeted and how they function are poorly understood.The MORC ATPases share a similar domain arrangement. The N terminus contains a GHKL (gyrase, heat-shock protein 90, histidine kinase, MutL) type ATPase domain, and at the C terminus is a coiled-coil segment. MORCs have been reported to form functional homomultimers or heteromultimers, where multimerization is likely mediated by the N-and/or the C-terminal domains (4, 6, 7). The coiled-coil region has been proposed to promote constitutive dimerization, whereas N-terminal ATPase head dimerization occurs only on ATP binding (6). This is consistent with other GHKL ATPases described in the literature, many of which have been reported to undergo ATP-dependent dimerization (8-10). Both plant and animal MORCs are capable of forming nuclear bodies, and mutations that impair ATP binding and/or hydrolysis disrupt nuclear body formation of human MORC3 (6).Animal MORCs also carry a CW-type zinc finger domain, which has been proposed to read histone H3 lysine 4 (H3K4) dimethylation and trimethylation mark...

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Section: Resultsmentioning

confidence: 99%

Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin

Yen

Pastor

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…They are crucial for chromosome segregation in a number of bacteria and feature a highly unusual architecture (Figure 4a) [53]. They consist of a long intramolecular, antiparallel coiled-coil that is linked to a hinge domain at one end and an ABC-type ATPase head domain at the other.…”

Section: Smc: Dna Bridges or Framework Structures For Dna Loop Extrusmentioning

confidence: 99%

Multilayer chromosome organization through DNA bending, bridging and extrusion

Gruber

2014

Current Opinion in Microbiology

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All living cells have to master the extraordinarily extended and tangly nature of genomic DNA molecules — in particular during cell division when sister chromosomes are resolved from one another and confined to opposite halves of a cell. Bacteria have evolved diverse sets of proteins, which collectively ensure the formation of compact and yet highly dynamic nucleoids. Some of these players act locally by changing the path of DNA through the bending of its double helical backbone. Other proteins have wider or even global impact on chromosome organization, for example by interconnecting two distant segments of chromosomal DNA or by actively relocating DNA within a cell. Here, I highlight different modes of chromosome organization in bacteria and on this basis consider models for the function of SMC protein complexes, whose mechanism of action is only poorly understood so far.

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“…S1). A coiled coil region separated by a hinge is a hallmark of SMC proteins (32). EptD shows similarity to a conserved hypothetical protein with unknown function (33).…”

Section: Bioinformatic Analysis Of Eptc Reveals Homology To Smc Protementioning

confidence: 99%

Noncanonical SMC protein in Mycobacterium smegmatis restricts maintenance of Mycobacterium fortuitum plasmids

Panas

Jain

Yang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Research on tuberculosis and leprosy was revolutionized by the development of a plasmid transformation system in the fast-growing surrogate, Mycobacterium smegmatis. This transformation system was made possible by the successful isolation of a M. smegmatis mutant strain mc 2 155, whose efficient plasmid transformation (ept) phenotype supported the replication of Mycobacterium fortuitum pAL5000 plasmids. In this report, we identified the EptC gene, the loss of which confers the ept phenotype. EptC shares significant amino acid sequence homology and domain structure with the MukB protein of Escherichia coli, a structural maintenance of chromosomes (SMC) protein. Surprisingly, M. smegmatis has three paralogs of SMC proteins: EptC and MSMEG_0370 both share homology with Gramnegative bacterial MukB; and MSMEG_2423 shares homology with Gram-positive bacterial SMCs, including the single SMC protein predicted for Mycobacterium tuberculosis and Mycobacterium leprae. Purified EptC was shown to bind ssDNA and stabilize negative supercoils in plasmid DNA. Moreover, an EptC-mCherry fusion protein was constructed and shown to bind to DNA in live mycobacteria, and to prevent segregation of plasmid DNA to daughter cells. To our knowledge, this is the first report of impaired plasmid maintenance caused by a SMC homolog, which has been canonically known to assist the segregation of genetic materials.plasmid segregation | electroporation | DNA topology | partition errors | cell division

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The bacterial chromosome: architecture and action of bacterial SMC and SMC-like complexes

Cited by 146 publications

References 93 publications

Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin

Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin

Multilayer chromosome organization through DNA bending, bridging and extrusion

Noncanonical SMC protein in Mycobacterium smegmatis restricts maintenance of Mycobacterium fortuitum plasmids

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