The maintenance of chromosome structure: positioning and functioning of SMC complexes

Jeppsson, Kristian; Kanno, Takaharu; Shirahige, Katsuhiko; Sjögren, Camilla

doi:10.1038/nrm3857

Cited by 197 publications

(188 citation statements)

References 165 publications

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“…This experiment demonstrates that label-free live cell imaging with SRS is a powerful method to examine chromosome dynamics during cell division. With this approach, it is also possible to observe nucleolus disassembly and reassembly, to determine the condensation level of DNA, and to monitor the movement of the chromosome during cell division, as well as other crucial cellular processes (25).…”

Section: Resultsmentioning

confidence: 99%

Label-free DNA imaging in vivo with stimulated Raman scattering microscopy

Lü

Basu

Igras

et al. 2015

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

255

213

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Label-free DNA imaging is highly desirable in biology and medicine to perform live imaging without affecting cell function and to obtain instant histological tissue examination during surgical procedures. Here we show a label-free DNA imaging method with stimulated Raman scattering (SRS) microscopy for visualization of the cell nuclei in live animals and intact fresh human tissues with subcellular resolution. Relying on the distinct Raman spectral features of the carbon-hydrogen bonds in DNA, the distribution of DNA is retrieved from the strong background of proteins and lipids by linear decomposition of SRS images at three optimally selected Raman shifts. Based on changes on DNA condensation in the nucleus, we were able to capture chromosome dynamics during cell division both in vitro and in vivo. We tracked mouse skin cell proliferation, induced by drug treatment, through in vivo counting of the mitotic rate. Furthermore, we demonstrated a label-free histology method for human skin cancer diagnosis that provides comparable results to other conventional tissue staining methods such as H&E. Our approach exhibits higher sensitivity than SRS imaging of DNA in the fingerprint spectral region. Compared with spontaneous Raman imaging of DNA, our approach is three orders of magnitude faster, allowing both chromatin dynamic studies and label-free optical histology in real time.

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Section: Resultsmentioning

confidence: 99%

Label-free DNA imaging in vivo with stimulated Raman scattering microscopy

Lü

Basu

Igras

et al. 2015

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

255

213

View full text Add to dashboard Cite

show abstract

“…However, no defects in TOP2A localization were observed, which corresponds to what has been reported for Smc5 cKO in mouse embryonic stem cells (Pryzhkova and Jordan, 2016). Studies of yeast SMC5/6 have shown that the complex is linked with TopoIIdependent catenation/decatenation functions (Jeppsson et al, 2014;Kanno et al, 2015;Kegel et al, 2011). Furthermore, meiotic depletion of Top2 in budding yeast affects Smc5 localization (Copsey et al, 2013).…”

Section: Smc5 Is a Maternal-effect Genementioning

confidence: 85%

SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes

et al. 2017

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SMC complexes include three major classes: cohesin, condensin and SMC5/6. However, the localization pattern and genetic requirements for the SMC5/6 complex during mammalian oogenesis have not previously been examined. In mouse oocytes, the SMC5/6 complex is enriched at the pericentromeric heterochromatin, and also localizes along chromosome arms during meiosis. The infertility phenotypes of females with a Zp3-Cre-driven conditional knockout (cKO) of Smc5 demonstrated that maternally expressed SMC5 protein is essential for early embryogenesis. Interestingly, protein levels of SMC5/6 complex components in oocytes decline as wild-type females age. When SMC5/6 complexes were completely absent in oocytes during meiotic resumption, homologous chromosomes failed to segregate accurately during meiosis I. Despite what appears to be an inability to resolve concatenation between chromosomes during meiosis, localization of topoisomerase IIα to bivalents was not affected; however, localization of condensin along the chromosome axes was perturbed. Taken together, these data demonstrate that the SMC5/6 complex is essential for the formation of segregation-competent bivalents during meiosis I, and findings suggest that age-dependent depletion of the SMC5/6 complex in oocytes could contribute to increased incidence of oocyte aneuploidy and spontaneous abortion in aging females.

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“…The SMC5/6 complex contains the Nse2/Mms21 E3 SUMO ligase as well as Nse1, an E3 ubiquitin ligase, and the Nse3-6 subunits (Supplemental Fig. S5a; Jeppsson et al 2014). High-throughput yeast two-hybrid (Y2H) screens suggested that budding yeast Nse5 might bind Slx5 (Hazbun et al 2003), like its Schizosaccharomyces pombe homolog (Prudden et al 2007).…”

Section: The Soluble Mps3nmentioning

confidence: 99%

PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL

et al. 2016

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High-resolution imaging shows that persistent DNA damage in budding yeast localizes in distinct perinuclear foci for repair. The signals that trigger DNA double-strand break (DSB) relocation or determine their destination are unknown. We show here that DSB relocation to the nuclear envelope depends on SUMOylation mediated by the E3 ligases Siz2 and Mms21. In G1, a polySUMOylation signal deposited coordinately by Mms21 and Siz2 recruits the SUMO targeted ubiquitin ligase Slx5/Slx8 to persistent breaks. Both Slx5 and Slx8 are necessary for damage relocation to nuclear pores. When targeted to an undamaged locus, however, Slx5 alone can mediate relocation in G1-phase cells, bypassing the requirement for polySUMOylation. In contrast, in S-phase cells, monoSUMOylation mediated by the Rtt107-stabilized SMC5/6-Mms21 E3 complex drives DSBs to the SUN domain protein Mps3 in a manner independent of Slx5. Slx5/Slx8 and binding to pores favor repair by ectopic break-induced replication and imprecise end-joining.

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The maintenance of chromosome structure: positioning and functioning of SMC complexes

Cited by 197 publications

References 165 publications

Label-free DNA imaging in vivo with stimulated Raman scattering microscopy

Label-free DNA imaging in vivo with stimulated Raman scattering microscopy

SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes

PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL

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