Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO). Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs) selected in the dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated by Rad52-, Rrm3- and Pol32-dependent break-induced replication. Combining mms21-CH with sgs1Δ caused a synergistic increase in GCRs rates, indicating the distinct roles of Mms21 and Sgs1 in suppressing GCRs. The mms21-CH mutation also caused increased rates of accumulating uGCRs mediated by breakpoints in unique sequences as revealed by whole genome sequencing. Consistent with the accumulation of endogenous DNA lesions, mms21-CH mutants accumulate increased levels of spontaneous Rad52 and Ddc2 foci and had a hyper-activated DNA damage checkpoint. Together, these findings support that Mms21 prevents the accumulation of spontaneous DNA lesions that cause diverse GCRs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860785 | PMC |
| http://dx.doi.org/10.1371/journal.pgen.1007250 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Relocation of Collapsed Forks to the Nuclear Pore Complex Depends on Sumoylation of DNA Repair Proteins and Permits Rad51 Association.
Cell Rep
May 2020
Department of Biology, Tufts University, Medford, MA 02155, USA; Program in Genetics, Tufts University, Boston, MA 02111, USA. Electronic address:
Expanded CAG repeats form stem-loop secondary structures that lead to fork stalling and collapse. Previous work has shown that these collapsed forks relocalize to nuclear pore complexes (NPCs) in late S phase in a manner dependent on replication, the nucleoporin Nup84, and the Slx5 protein, which prevents repeat fragility and instability. Here, we show that binding of the Smc5/6 complex to the collapsed fork triggers Mms21-dependent sumoylation of fork-associated DNA repair proteins, and that RPA, Rad52, and Rad59 are the key sumoylation targets that mediate relocation.
View Article and Find Full Text PDFMms21: A Putative SUMO E3 Ligase in That Negatively Regulates Invasiveness and Filamentation, and Is Required for the Genotoxic and Cellular Stress Response.
Genetics
February 2019
Department of Biology, Concordia University, Montreal, Quebec H4B 1R6, Canada
In the life cycle of the fungal pathogen , the formation of filamentous cells is a differentiation process that is critically involved in host tissue invasion, and in adaptation to host cell and environmental stresses. Here, we have used the Gene Replacement And Conditional Expression library to identify genes controlling invasiveness and filamentation; conditional repression of the library revealed 69 mutants that triggered these processes. Intriguingly, the genes encoding the small ubiquitin-like modifier (SUMO) E3 ligase Mms21, and all other tested members of the sumoylation pathway, were both nonessential and capable of triggering filamentation upon repression, suggesting an important role for sumoylation in controlling filamentation in We have investigated Mms21 in detail.
View Article and Find Full Text PDFLocal activation of mammalian separase in interphase promotes double-strand break repair and prevents oncogenic transformation.
EMBO J
November 2018
Chair of Genetics, University of Bayreuth, Bayreuth, Germany
Separase halves eukaryotic chromosomes in M-phase by cleaving cohesin complexes holding sister chromatids together. Whether this essential protease functions also in interphase and/or impacts carcinogenesis remains largely unknown. Here, we show that mammalian separase is recruited to DNA double-strand breaks (DSBs) where it is activated to locally cleave cohesin and facilitate homology-directed repair (HDR).
View Article and Find Full Text PDFSUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements.
PLoS Genet
March 2018
Ludwig Institute for Cancer Research, University of California School of Medicine, San Diego, La Jolla, California, United States of America.
Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO). Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs) selected in the dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated by Rad52-, Rrm3- and Pol32-dependent break-induced replication.
View Article and Find Full Text PDFInterplay between Top1 and Mms21/Nse2 mediated sumoylation in stable maintenance of long chromosomes.
Curr Genet
August 2017
Department of Biochemistry, Indian Institute of Science, C. V. Raman Avenue, Bangalore, Karnataka, 560012, India.
Genetic information in cells is encrypted in DNA molecules forming chromosomes of varying sizes. Accurate replication and partitioning of chromosomes in the crowded cellular milieu is a complex process involving duplication, folding and movement. Longer chromosomes may be more susceptible to mis-segregation or DNA damage and there may exist specialized physiological mechanisms preventing this.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!