Symmetric control of sister chromatid cohesion establishment.

Abstract Besides entrapping sister chromatids, cohesin drives other high-order chromosomal structural dynamics like looping, compartmentalization and condensation. ESCO2 acetylates a subset of cohesin so that cohesion must be established and only be established between nascent sister chromatids. How this process is precisely achieved remains unknown. Here, we report that GSK3 family kinases provide higher hierarchical control through an ESCO2 regulator, CRL4MMS22L. GSK3s phosphorylate Thr105 in MMS22L, resulting in homo-dimerization of CRL4MMS22L and ESCO2 during S phase as evidenced by single-molecule spectroscopy and several biochemical approaches. A single phospho-mimicking mutation on MMS22L (T105D) is sufficient to mediate their dimerization and rescue the cohesion defects caused by GSK3 or MMS22L depletion, whereas non-phosphorylable T105A exerts dominant-negative effects even in wildtype cells. Through cell fractionation and time-course measurements, we show that GSK3s facilitate the timely chromatin association of MMS22L and ESCO2 and subsequently SMC3 acetylation. The necessity of ESCO2 dimerization implicates symmetric control of cohesion establishment in eukaryotes.

[1]  I. Onn,et al.  It’s all in the numbers: Cohesin stoichiometry , 2022, Frontiers in Molecular Biosciences.

[2]  P. V. van Haastert,et al.  Combined FCS and PCH Analysis to Quantify Protein Dimerization in Living Cells , 2021, International journal of molecular sciences.

[3]  Hongtao Yu,et al.  Shaping of the 3D genome by the ATPase machine cohesin , 2020, Experimental & Molecular Medicine.

[4]  M. Dong,et al.  The acetyltransferase Eco1 elicits cohesin dimerization during S phase , 2020, The Journal of Biological Chemistry.

[5]  J. Irudayaraj,et al.  Monomeric cohesin state revealed by live‐cell single‐molecule spectroscopy , 2019, EMBO reports.

[6]  K. Nasmyth,et al.  Organization of Chromosomal DNA by SMC Complexes. , 2019, Annual review of genetics.

[7]  Haitao Sun,et al.  Cul4-Ddb1 ubiquitin ligases facilitate DNA replication-coupled sister chromatid cohesion through regulation of cohesin acetyltransferase Esco2 , 2018, bioRxiv.

[8]  A. Losada,et al.  Establishing and dissolving cohesion during the vertebrate cell cycle. , 2018, Current opinion in cell biology.

[9]  Rongsheng Tong,et al.  Nuclear GSK3β induces DNA double-strand break repair by phosphorylating 53BP1 in glioblastoma , 2018, International journal of oncology.

[10]  D. Morgan,et al.  Firing of Replication Origins Frees Dbf4-Cdc7 to Target Eco1 for Destruction , 2017, Current Biology.

[11]  K. Shirahige,et al.  Rtt101‐Mms1‐Mms22 coordinates replication‐coupled sister chromatid cohesion and nucleosome assembly , 2017, EMBO reports.

[12]  A. Gingras,et al.  Acetylation of PCNA Sliding Surface by Eco1 Promotes Genome Stability through Homologous Recombination. , 2017, Molecular cell.

[13]  L. Karnitz,et al.  Glycogen Synthase Kinase 3 (GSK-3)-mediated Phosphorylation of Uracil N-Glycosylase 2 (UNG2) Facilitates the Repair of Floxuridine-induced DNA Lesions and Promotes Cell Survival* , 2016, The Journal of Biological Chemistry.

[14]  P. Kursula,et al.  Sister Chromatid Cohesion Establishment Factor ESCO1 Operates by Substrate-Assisted Catalysis. , 2016, Structure.

[15]  V. Guacci,et al.  Interallelic complementation provides functional evidence for cohesin–cohesin interactions on DNA , 2015, Molecular biology of the cell.

[16]  Hongtao Yu,et al.  Regulation of sister chromatid cohesion during the mitotic cell cycle , 2015, Science China Life Sciences.

[17]  K. Shirahige,et al.  Esco1 Acetylates Cohesin via a Mechanism Different from That of Esco2 , 2015, Current Biology.

[18]  R. Jope,et al.  Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. , 2015, Pharmacology & therapeutics.

[19]  R. Skibbens,et al.  Cohesin without Cohesion: A Novel Role for Pds5 in Saccharomyces cerevisiae , 2014, PloS one.

[20]  F. Pilot-Storck,et al.  Phosphorylation of NBR1 by GSK3 modulates protein aggregation , 2014, Autophagy.

[21]  Le Cong,et al.  Multiplex Genome Engineering Using CRISPR/Cas Systems , 2013, Science.

[22]  Duncan J. Smith,et al.  An Eco1-independent sister chromatid cohesion establishment pathway in S. cerevisiae , 2013, Chromosoma.

[23]  Frank Uhlmann,et al.  An Eco1-independent sister chromatid cohesion establishment pathway in S. cerevisiae , 2013, Chromosoma.

[24]  John R. Yates,et al.  Sequential Primed Kinases Create a Damage-Responsive Phosphodegron on Eco1 , 2012, Nature Structural &Molecular Biology.

[25]  J. Peters,et al.  Sister chromatid cohesion. , 2012, Cold Spring Harbor perspectives in biology.

[26]  Barry P. Young,et al.  The Mck1 GSK-3 kinase inhibits the activity of Clb2-Cdk1 post-nuclear division , 2012, Cell cycle.

[27]  Jingrong Chen,et al.  Cohesin Acetylation Promotes Sister Chromatid Cohesion Only in Association with the Replication Machinery* , 2012, The Journal of Biological Chemistry.

[28]  Vipin T. Sreedharan,et al.  Cohesin Rings Devoid of Scc3 and Pds5 Maintain Their Stable Association with the DNA , 2012, PLoS genetics.

[29]  Joanne I. Yeh,et al.  Damaged DNA induced UV-damaged DNA-binding protein (UV-DDB) dimerization and its roles in chromatinized DNA repair , 2012, Proceedings of the National Academy of Sciences.

[30]  I. Willis,et al.  TOR signaling regulates ribosome and tRNA synthesis via LAMMER/Clk and GSK-3 family kinases. , 2012, Molecular cell.

[31]  Nicholas A. Lyons,et al.  Cdk1-dependent destruction of Eco1 prevents cohesion establishment after S phase. , 2011, Molecular cell.

[32]  A. Gronenborn,et al.  The Cullin-RING E3 ubiquitin ligase CRL4-DCAF1 complex dimerizes via a short helical region in DCAF1. , 2011, Biochemistry.

[33]  P. Jallepalli,et al.  Sister acts: coordinating DNA replication and cohesion establishment. , 2010, Genes & development.

[34]  A. Hyman,et al.  Sororin Mediates Sister Chromatid Cohesion by Antagonizing Wapl , 2010, Cell.

[35]  K. Nasmyth,et al.  An Smc3 acetylation cycle is essential for establishment of sister chromatid cohesion. , 2010, Molecular cell.

[36]  Helen R. Flynn,et al.  Hos1 deacetylates Smc3 to close the cohesin acetylation cycle. , 2010, Molecular cell.

[37]  J. Gerton,et al.  Regulators of the cohesin network. , 2010, Annual review of biochemistry.

[38]  Kim Nasmyth,et al.  Cohesin: its roles and mechanisms. , 2009, Annual review of genetics.

[39]  V. Guacci,et al.  The zinc finger of Eco1 enhances its acetyltransferase activity during sister chromatid cohesion , 2009, Nucleic acids research.

[40]  L. Pintard,et al.  Regulation of cullin-RING E3 ubiquitin-ligases by neddylation and dimerization , 2009, Cellular and Molecular Life Sciences.

[41]  P. Rao,et al.  A handcuff model for the cohesin complex , 2008, The Journal of cell biology.

[42]  Philip East,et al.  Eco1-Dependent Cohesin Acetylation During Establishment of Sister Chromatid Cohesion , 2008, Science.

[43]  Steven P. Gygi,et al.  A Molecular Determinant for the Establishment of Sister Chromatid Cohesion , 2008, Science.

[44]  Xuewen Pan,et al.  Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast. , 2008, Molecular cell.

[45]  E. Foss,et al.  Hst3 Is Regulated by Mec1-dependent Proteolysis and Controls the S Phase Checkpoint and Sister Chromatid Cohesion by Deacetylating Histone H3 at Lysine 56* , 2007, Journal of Biological Chemistry.

[46]  B. Doble,et al.  Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism. , 2007, Cell metabolism.

[47]  Trisha N Davis,et al.  In vivo analysis of cohesin architecture using FRET in the budding yeast Saccharomyces cerevisiae , 2007, The EMBO journal.

[48]  T. Hirano,et al.  Human Wapl Is a Cohesin-Binding Protein that Promotes Sister-Chromatid Resolution in Mitotic Prophase , 2006, Current Biology.

[49]  S. Jentsch,et al.  PCNA controls establishment of sister chromatid cohesion during S phase. , 2006, Molecular cell.

[50]  H. Zou,et al.  Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion. , 2005, Molecular biology of the cell.

[51]  T. Hirano,et al.  Functional contribution of Pds5 to cohesin-mediated cohesion in human cells and Xenopus egg extracts , 2005, Journal of Cell Science.

[52]  T. Itoh,et al.  Cohesin relocation from sites of chromosomal loading to places of convergent transcription , 2004, Nature.

[53]  K. Nasmyth,et al.  Chromosomal Cohesin Forms a Ring , 2003, Cell.

[54]  Taekjip Ha,et al.  Initiation and re-initiation of DNA unwinding by the Escherichia coli Rep helicase , 2002, Nature.

[55]  Kim Nasmyth,et al.  Molecular architecture of SMC proteins and the yeast cohesin complex. , 2002, Molecular cell.

[56]  Karl Mechtler,et al.  Eco1 Is a Novel Acetyltransferase that Can Acetylate Proteins Involved in Cohesion , 2002, Current Biology.

[57]  P. Cohen,et al.  The renaissance of GSK3 , 2001, Nature Reviews Molecular Cell Biology.

[58]  P. Hieter,et al.  Ctf7p is essential for sister chromatid cohesion and links mitotic chromosome structure to the DNA replication machinery. , 1999, Genes & development.

[59]  Wenjuan Wang,et al.  Supporting Information Single-Molecule Photoactivation FRET: A General and Easy-to- Implement Approach to Break the Concentration Barrier , 2017 .

[60]  H. Nishitani,et al.  Chromatin fractionation analysis of licensing factors in mammalian cells. , 2014, Methods in molecular biology.

[61]  A. Visser,et al.  Global analysis of autocorrelation functions and photon counting distributions. , 2011, Frontiers in bioscience.

[62]  J. Woodgett,et al.  Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. , 2000, Nature.