Structural and Functional Insights into the Roles of the Mms21 Subunit of the Smc5/6 Complex

Duan, Xinyuan; Sarangi, Prabha; Liu, Xianpeng; Rangi, Gurdish K.; Zhao, Xiaolan; Hong, Ye

doi:10.1016/j.molcel.2009.06.032

Cited by 90 publications

(124 citation statements)

References 37 publications

Supporting

Mentioning

115

Contrasting

Order By: Relevance

“…The localization of Mms21 on the coiled-coil arm of Smc5 is adjacent to the Nse5/Nse6-binding site at the hinge domain of the complex (25,26), and this led us to question whether Nse5 FIGURE 1. Nse5 temperature-sensitive alleles nse5-ts1 and nse5-ts2 are unable to interact with SUMO and are defective in Smc5 sumoylation.…”

Section: Nse5 Interacts With Sumo and Is Required For Smc5mentioning

confidence: 99%

See 1 more Smart Citation

During Replication Stress, Non-Smc Element 5 (Nse5) Is Required for Smc5/6 Protein Complex Functionality at Stalled Forks

Bustard

Menolfi

Jeppsson

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: The Smc5/6 complex has six non-SMC elements, including Nse5. Results: Utilizing two mutants of NSE5, we separated Smc5 sumoylation from Smc5/6 complex function. Conclusion: Nse5 integrity is important for Smc5/6 complex stability, which in turn is essential for localization of the complex to stalled forks. Significance: Our results provide the first in vivo characterization of Nse5 for Smc5/6 complex function.

show abstract

Section: Nse5 Interacts With Sumo and Is Required For Smc5mentioning

confidence: 99%

“…The essential function of Mms21 is not its E3 ligase activity because mms21-11 mutant cells, lacking ligase activity, grow well in the absence of DNA-damaging agents. By contrast, the full disruption of Mms21 is lethal (19,20,25).…”

mentioning

confidence: 99%

During Replication Stress, Non-Smc Element 5 (Nse5) Is Required for Smc5/6 Protein Complex Functionality at Stalled Forks

Bustard

Menolfi

Jeppsson

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…MMS21 (for methyl methanesulfonate sensitivity gene21) encodes a SUMO E3 ligase that forms a critical component of the STRUCTURAL MAINTENANCE OF CHROMOSOMES5/6 (SMC5/6) complex, which is an evolutionarily conserved chromosomal ATPase required for cell growth and DNA repair (Duan et al, 2009). The SUMO ligase activity of MMS21 contributes to the roles of the SMC5/6 complex in recombinational repair, collapsed replication fork restart, and ribosomal DNA and telomere maintenance, with some relevant substrates having been identified (Potts and Yu, 2005;Zhao and Blobel, 2005).…”

mentioning

confidence: 99%

AtMMS21, an SMC5/6 Complex Subunit, Is Involved in Stem Cell Niche Maintenance and DNA Damage Responses in Arabidopsis Roots

Yuan

Liu

et al. 2013

Plant Physiology

View full text Add to dashboard Cite

Plants maintain stem cells in meristems to sustain lifelong growth; these stem cells must have effective DNA damage responses to prevent mutations that can propagate to large parts of the plant. However, the molecular links between stem cell functions and DNA damage responses remain largely unexplored. Here, we report that the small ubiquitin-related modifier E3 ligase AtMMS21 (for methyl methanesulfonate sensitivity gene21) acts to maintain the root stem cell niche by mediating DNA damage responses in Arabidopsis (Arabidopsis thaliana). Mutation of AtMMS21 causes defects in the root stem cell niche during embryogenesis and postembryonic stages. AtMMS21 is essential for the proper expression of stem cell niche-defining transcription factors. Moreover, mms21-1 mutants are hypersensitive to DNA-damaging agents, have a constitutively increased DNA damage response, and have more DNA double-strand breaks (DSBs) in the roots. Also, mms21-1 mutants exhibit spontaneous cell death within the root stem cell niche, and treatment with DSB-inducing agents increases this cell death, suggesting that AtMMS21 is required to prevent DSB-induced stem cell death. We further show that AtMMS21 functions as a subunit of the STRUCTURAL MAINTENANCE OF CHROMOSOMES5/6 complex, an evolutionarily conserved chromosomal ATPase required for DNA repair. These data reveal that AtMMS21 acts in DSB amelioration and stem cell niche maintenance during Arabidopsis root development.

show abstract

“…cerevisiae has four SUMO-E3 ligases. Siz1 is responsible for the majority of SUMOylation during vegetative growth, with Siz2 conducting most of the remainder (39); Mms21 directs SUMOylation of proteins involved in chromosome maintenance and recombination (40,(42)(43)(44)(45)(46). MMS21 is an essential gene because Mms21 plays a critical role in the structural maintenance of chromosomes (SMC) protein complex.…”

mentioning

confidence: 99%

SUMOylation regulates the SNF1 protein kinase

Simpson-Lavy

Johnston

2013

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

View full text Add to dashboard Cite

The AMP-activated protein kinase (AMPK) is a major stress sensor of mammalian cells. AMPK's homolog in the yeast Saccharomyces cerevisiae, the SNF1 protein kinase, is a central regulator of carbon metabolism that inhibits the Snf3/Rgt2-Rgt1 glucose sensing pathway and activates genes involved in respiration. We present evidence that glucose induces modification of the Snf1 catalytic subunt of SNF1 with the small ubiquitin-like modifier protein SUMO, catalyzed by the SUMO (E3) ligase Mms21. Our results suggest that SUMOylation of Snf1 inhibits its function in two ways: by interaction of SUMO attached to lysine 549 with a SUMO-interacting sequence motif located near the active site of Snf1, and by targeting Snf1 for destruction via the Slx5-Slx8 (SUMO-directed) ubiquitin ligase. These findings reveal another way SNF1 function is regulated in response to carbon source.protein kinase regulation | protein modification | signal transduction G lucose is the preferred carbon source of most cells, including Saccharomyces cerevisiae, which ferments it to ethanol and CO 2 , producing only two ATPs, even when oxygen is available to drive production of much more ATP. This preference for fermentation (which cancer cells share), is known as the Crabtree or Warburg effect (1, 2). Because of the energetic inefficiency of fermentation, yeast cells must be adroit in sensing glucose. S. cerevisiae has three well-known glucose sensing pathways: (i) the Gpa1/2-Ras2-PKA pathway that regulates stress response (through Msn2/4) and other things; (ii) the SNF1 pathway, which regulates respiratory metabolism and other processes; and (iii) the Snf3/Rgt2-Rgt1 (SRR) pathway that regulates expression of genes encoding hexose transporters (3).The SRR (sensor/receptor-repressor) pathway begins at the cell surface with high-affinity (Snf3) (4) and low-affinity (Rgt2) glucose sensors (5) that are coupled to the casein kinases Yck1 and Yck2, which catalyze phosphorylation of the corepressor proteins Mth1 and Std1 (6), leading to their ubiquitinylation by SCF Grr1 (7,8). The subsequent destruction of Mth1 and Std1 inactivates the Rgt1 transcriptional repressor, resulting in derepression of HXT genes encoding hexose transporters (7, 9). In response to glucose, Yck1/2 also mediates inactivation and degradation of transporters of alternative carbon sources, such as maltose (Mal61) (10) and lactate/pyruvate/acetate (Jen1) (11). Achieving this glucose-induced switching of transporters seems to be the main purpose of the SRR pathway (12).The SNF1 protein kinase-the ortholog of the AMP-activated protein kinase (AMPK), a major stress-activated protein kinase in mammalian cells (13,14)-is a central regulator of carbon metabolism (15,16). This kinase is an activator of Adr1 and Cat8, which activate expression of genes involved in the diauxic shift, ethanol, and lactate uptake and catabolism, gluconeogenesis, and respiration (17-21), and is an inhibitor of the Mig1 repressor of glucose-repressed genes (22). SNF1 is a heterotrimer of the Snf1 catalytic subunit,...

show abstract

Structural and Functional Insights into the Roles of the Mms21 Subunit of the Smc5/6 Complex

Cited by 90 publications

References 37 publications

During Replication Stress, Non-Smc Element 5 (Nse5) Is Required for Smc5/6 Protein Complex Functionality at Stalled Forks

During Replication Stress, Non-Smc Element 5 (Nse5) Is Required for Smc5/6 Protein Complex Functionality at Stalled Forks

AtMMS21, an SMC5/6 Complex Subunit, Is Involved in Stem Cell Niche Maintenance and DNA Damage Responses in Arabidopsis Roots

SUMOylation regulates the SNF1 protein kinase

Contact Info

Product

Resources

About