Faithful chromosome segregation requires that the sister chromatids be disjoined completely. Defective disjunction can lead to the persistence of histone-free threads of DNA known as ultra-fine bridges (UFBs) that connect the separating sister DNA molecules during anaphase. UFBs arise at specific genomic loci and can only be visualized by detection of associated proteins such as PICH, BLM, topoisomerase IIIα, and RPA. However, it remains unknown how these proteins work together to promote UFB processing. We used a combination of ensemble biochemistry and new single-molecule assays to reconstitute key steps of UFB recognition and processing by these human proteins in vitro. We discovered characteristic patterns of hierarchical recruitment and coordinated biochemical activities that were specific for DNA structures modeling UFBs arising at either centromeres or common fragile sites. Our results describe a mechanistic model for how unresolved DNA replication structures are processed by DNA-structure-specific binding factors in mitosis to prevent pathological chromosome nondisjunction.
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Source data are available for Figs. 2, 5, and 6 and Supplementary Figs. 1, 3, 4, and 7–9 with the paper online.
Thompson, S. L. & Compton, D. A. Chromosomes and cancer cells. Chromosome Res. 19, 433–444 (2011).
Herbert, M., Kalleas, D., Cooney, D., Lamb, M. & Lister, L. Meiosis and maternal aging: insights from aneuploid oocytes and trisomy births. Cold Spring Harb. Perspect. Biol. 7, a017970 (2015).
Mankouri, H. W., Huttner, D. & Hickson, I. D. How unfinished business from S-phase affects mitosis and beyond. EMBO J. 32, 2661–2671 (2013).
Durkin, S. G. & Glover, T. W. Chromosome fragile sites. Annu. Rev. Genet. 41, 169–192 (2007).
Glover, T. W., Wilson, T. E. & Arlt, M. F. Fragile sites in cancer: more than meets the eye. Nat. Rev. Cancer 17, 489–501 (2017).
Sarlós, K., Biebricher, A., Petermann, E. J. G., Wuite, G. J. L. & Hickson, I. D. Knotty problems during mitosis: mechanistic insight into the processing of ultrafine DNA bridges in anaphase. Cold Spring Harb. Symp. Quant. Biol. 82, 187–195 (2017).
Baumann, C., Körner, R., Hofmann, K. & Nigg, E. A. PICH, a centromere-associated SNF2 family ATPase, is regulated by Plk1 and required for the spindle checkpoint. Cell 128, 101–114 (2007).
Chan, K. L., North, P. S. & Hickson, I. D. BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges. EMBO J. 26, 3397–3409 (2007).
Cunniff, C., Bassetti, J. A. & Ellis, N. A. Bloom’s syndrome: clinical spectrum, molecular pathogenesis, and cancer predisposition. Mol. Syndromol 8, 4–23 (2017).
German, J., Sanz, M. M., Ciocci, S., Ye, T. Z. & Ellis, N. A. Syndrome-causing mutations of the BLM gene in persons in the Bloom’s Syndrome Registry. Hum. Mutat. 28, 743–753 (2007).
Wu, L. & Hickson, I. D. The Bloom’s syndrome helicase suppresses crossing over during homologous recombination. Nature 426, 870–874 (2003).
Bachrati, C. Z., Borts, R. H. & Hickson, I. D. Mobile D-loops are a preferred substrate for the Bloom’s syndrome helicase. Nucleic Acids Res. 34, 2269–2279 (2006).
Martin, C. A. et al. Mutations in TOP3A cause a Bloom’s syndrome–like disorder. Am. J. Hum. Genet. 103, 221–231 (2018).
Goulaouic, H. et al. Purification and characterization of human DNA topoisomerase IIIα. Nucleic Acids Res. 27, 2443–2450 (1999).
Yang, J., Bachrati, C. Z., Ou, J., Hickson, I. D. & Brown, G. W. Human topoisomerase IIIα is a single-stranded DNA decatenase that is stimulated by BLM and RMI1. J. Biol. Chem. 285, 21426–21436 (2010).
Wu, L. et al. BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc. Natl. Acad. Sci. USA 103, 4068–4073 (2006).
Xu, D. et al. RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. Genes Dev. 22, 2843–2855 (2008).
Singh, T. R. et al. BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase–double Holliday junction dissolvasome. Genes Dev. 22, 2856–2868 (2008).
Yin, J. et al. BLAP75, an essential component of Bloom’s syndrome protein complexes that maintain genome integrity. EMBO J. 24, 1465–1476 (2005).
Vos, S. M., Tretter, E. M., Schmidt, B. H. & Berger, J. M. All tangled up: how cells direct, manage and exploit topoisomerase function. Nat. Rev. Mol. Cell Biol. 12, 827–841 (2011).
Nielsen, C. F. & Hickson, I. D. PICH promotes mitotic chromosome segregation: identification of a novel role in rDNA disjunction. Cell Cycle 15, 2704–2711 (2016).
Nielsen, C. F. et al. PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis. Nat. Commun. 6, 8962 (2015).
Chan, K. L., Palmai-Pallag, T., Ying, S. & Hickson, I. D. Replication stress induces sister-chromatid bridging at fragile site loci in mitosis. Nat. Cell Biol. 11, 753–760 (2009).
Barefield, C. & Karlseder, J. The BLM helicase contributes to telomere maintenance through processing of late-replicating intermediate structures. Nucleic Acids Res. 40, 7358–7367 (2012).
Burrell, R. A. et al. Replication stress links structural and numerical cancer chromosomal instability. Nature 494, 492–496 (2013).
Biebricher, A. et al. PICH: a DNA translocase specially adapted for processing anaphase bridge DNA. Mol. Cell 51, 691–701 (2013).
Chan, Y. W., Fugger, K. & West, S. C. Unresolved recombination intermediates lead to ultra-fine anaphase bridges, chromosome breaks and aberrations. Nat. Cell Biol. 20, 92–103 (2018).
Chan, K. L. & Hickson, I. D. On the origins of ultra-fine anaphase bridges. Cell Cycle 8, 3065–3066 (2009).
Hengeveld, R. C. C. et al. Rif1 is required for resolution of ultrafine DNA bridges in anaphase to ensure genomic stability. Dev. Cell 34, 466–474 (2015).
van Mameren, J. et al. Unraveling the structure of DNA during overstretching by using multicolor, single-molecule fluorescence imaging. Proc. Natl. Acad. Sci. USA 106, 18231–18236 (2009).
van Mameren, J. et al. Counting RAD51 proteins disassembling from nucleoprotein filaments under tension. Nature 457, 745–748 (2009).
Farge, G. et al. Protein sliding and DNA denaturation are essential for DNA organization by human mitochondrial transcription factor A. Nat. Commun. 3, 1013 (2012).
Brouwer, I. et al. Sliding sleeves of XRCC4–XLF bridge DNA and connect fragments of broken DNA. Nature 535, 566–569 (2016).
Wuite, G. J., Smith, S. B., Young, M., Keller, D. & Bustamante, C. Single-molecule studies of the effect of template tension on T7 DNA polymerase activity. Nature 404, 103–106 (2000).
Karow, J. K., Chakraverty, R. K. & Hickson, I. D. The Bloom’s syndrome gene product is a 3′–5′ DNA helicase. J. Biol. Chem. 272, 30611–30614 (1997).
Brosh, R. M. Jr. et al. Replication protein A physically interacts with the Bloom’s syndrome protein and stimulates its helicase activity. J. Biol. Chem. 275, 23500–23508 (2000).
Xue, X., Raynard, S., Busygina, V., Singh, A. K. & Sung, P. Role of replication protein A in double Holliday junction dissolution mediated by the BLM–Topo IIIα–RMI1–RMI2 protein complex. J. Biol. Chem. 288, 14221–14227 (2013).
Stark, W. M., Sherratt, D. J. & Boocock, M. R. Site-specific recombination by Tn3 resolvase: topological changes in the forward and reverse reactions. Cell 58, 779–790 (1989).
Harmon, F. G., Brockman, J. P. & Kowalczykowski, S. C. RecQ helicase stimulates both DNA catenation and changes in DNA topology by topoisomerase III. J. Biol. Chem. 278, 42668–42678 (2003).
Cejka, P., Plank, J. L., Dombrowski, C. C. & Kowalczykowski, S. C. Decatenation of DNA by the S. cerevisiae Sgs1–Top3–Rmi1 and RPA complex: a mechanism for disentangling chromosomes. Mol. Cell 47, 886–896 (2012).
Gaymes, T. J. et al. Increased error-prone non homologous DNA end-joining—a proposed mechanism of chromosomal instability in Bloom’s syndrome. Oncogene 21, 2525–2533 (2002).
Natsume, T., Kiyomitsu, T., Saga, Y. & Kanemaki, M. T. Rapid protein depletion in human cells by auxin-inducible degron tagging with short homology donors. Cell Rep. 15, 210–218 (2016).
Debatisse, M., Le Tallec, B., Letessier, A., Dutrillaux, B. & Brison, O. Common fragile sites: mechanisms of instability revisited. Trends Genet. 28, 22–32 (2012).
Suski, C. & Marians, K. J. Resolution of converging replication forks by RecQ and topoisomerase III. Mol. Cell 30, 779–789 (2008).
Trask, D. K., DiDonato, J. A. & Muller, M. T. Rapid detection and isolation of covalent DNA/protein complexes: application to topoisomerase I and II. EMBO J. 3, 671–676 (1984).
Kung, V. T. & Wang, J. C. Purification and characterization of an omega protein from Micrococcus luteus. J. Biol. Chem. 252, 5398–5402 (1977).
Smith, S. B., Cui, Y. & Bustamante, C. Overstretching B-DNA: the elastic response of individual double-stranded and single-stranded DNA molecules. Science 271, 795–799 (1996).
Candelli, A. et al. A toolbox for generating single-stranded DNA in optical tweezers experiments. Biopolymers 99, 611–620 (2013).
Porter, A. C. & Farr, C. J. Topoisomerase II: untangling its contribution at the centromere. Chromosome Res. 12, 569–583 (2004).
Strick, T. R., Croquette, V. & Bensimon, D. Single-molecule analysis of DNA uncoiling by a type II topoisomerase. Nature 404, 901–904 (2000).
Bizard, A. H. & Hickson, I. D. The dissolution of double Holliday junctions. Cold Spring Harb. Perspect. Biol. 6, a016477 (2014).
Krejci, L., Altmannova, V., Spirek, M. & Zhao, X. Homologous recombination and its regulation. Nucleic Acids Res. 40, 5795–5818 (2012).
Daley, J. M., Chiba, T., Xue, X., Niu, H. & Sung, P. Multifaceted role of the Topo IIIα–RMI1–RMI2 complex and DNA2 in the BLM-dependent pathway of DNA break end resection. Nucleic Acids Res 42, 11083–11091 (2014).
Candelli, A., Wuite, G. J. L. & Peterman, E. J. G. Combining optical trapping, fluorescence microscopy and micro-fluidics for single molecule studies of DNA–protein interactions. Phys. Chem. Chem. Phys. 13, 7263–7272 (2011).
Krasnow, M. A. & Cozzarelli, N. R. Site-specific relaxation and recombination by the Tn3 resolvase: recognition of the DNA path between oriented res sites. Cell 32, 1313–1324 (1983).
Brown, T. Southern blotting. Curr. Protoc. Immunol. Chapter 10, Unit 10.6A (2001).
Bachrati, C. Z. & Hickson, I. D. Dissolution of double Holliday junctions by the concerted action of BLM and topoisomerase IIIα. Methods Mol. Biol. 582, 91–102 (2009).
We thank G. King for helpful discussions, H. Mankouri for helpful comments on the manuscript, M. Nadal (Institut Jacques Monod) for the Sulfolobus solfactarius TopA, and M. Kanemaki (National Institute of Genetics, Japan) for development of the TopoIII protein degron system. Work in the authors’ laboratories is supported by the Danish National Research Fund (DNRF115), the European Union Horizon 2020 Programme ‘Chromavision’ (665233), the European Research Council, the Human Frontier Science Program, the Netherlands Organization for Scientific Research (NWO; ‘Catching PICH in the Act’ project number 741.015.002), the French National Research Agency, and the French National Cancer Institute.
The authors declare no competing interests.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Integrated supplementary information
a, SDS–PAGE of the recombinant proteins used in this study. Lanes: 1, BLM; 2, BLMSNAP (fluorescent BLM variant labeled with the red dye SNAP-Surface 649); 3, TRR (subunits marked); 4, TRRCherry (fluorescent TRR variant labeled with mCherry; subunits marked); 5, PICH; 6, PICHGFP (fluorescent PICH variant labeled with eGFP); 7, PICHK128A-GFP; 8, RPA (subunits marked); 9, RPAStrawberry (subunits marked); 10, TRRY337F-Cherry (subunits marked). b–d, Examples of fluorescence bleaching traces of three different fluorophores used in the optical tweezers experiments (eGFP (b), SNAP649 (c), mCherry (d)). Bleaching is characterized by a sudden drop of fluorescence to background level, and different traces for the same chromophore display very similar brightness levels. Both these features are characteristic with fluorescence emitted from single dye molecules. Note that trace I in c drops after the first two frames from an intensity of ~40 to ~20; this indicates that initially two dye molecules were present and that the first one bleached after 2 s, whereas the second one bleached after 16 s. e, The exonuclease activity of the T7 polymerase can be utilized to generate tracks of defined ssDNA length on an initially fully dsDNA molecule. The amount of ssDNA can be deduced from the force-extension curves (shown here are examples of dsDNA (black), ssDNA (blue), as well as single-stranded and double-stranded DNA resulting from exonuclease activity (red). f–i, Fluorescence snapshots (left) and schematic representation (right) of the DNA binding of BLMSNAP and TRRCherry when the DNA is incubated with the protein alone in the single-molecule assays. Data were collected using either fully double-stranded (f and h) or a partial single-stranded and double-stranded molecule generated using T7 DNA polymerase (g and i). j,k, Similar to RPA, the binding of TRR and BLM to ssDNA is not sensitive to applied forces. j, A dsDNA molecule that is put under very high tension (~65 pN) in the buffer channel for an extended period generates ssDNA sections by fraying of the DNA from the open ends and from any nicks. After incubation with labeled TRR, the fluorescence snapshot shows three homogeneously bright sections that are separated by very bright spots (red arrows) from two dark regions on the DNA. The bright sections signify ssDNA under tension, whereas the frayed ssDNA is not under tension and therefore appears as a very bright, compact spot (ssDNA in a tight coil) at the junction with dsDNA (dark) sections. k, Alternatively, if high tension is applied to a dsDNA molecule in the protein channel (BLM in this case), the protein binds rapidly to internally forming ssDNA (denoted ‘bubbles’; green arrows). Since bubbles form throughout the dsDNA molecule, the fluorescence pattern is patchy compared to that in j. The strong binding of both proteins to ssDNA under high tension indicates that, similar to RPA, their binding properties are not sensitive to DNA tension
a, Immunofluorescence image of a cUFB visualized by staining for PICH (green) and for the centromere-specific histone variant CENPA (red), which marks the termini of cUFBs. Scale bar, 2 μm. b, Fluorescence snapshots of BLMSNAP, TRR (non-labeled), and RPAStrawberry binding a dsDNA molecule before (1) and after (3) coating with PICHGFP (2). c, Schematic representation of the data in b (BLM, blue; TRR, white; RPA, red; PICH, green). d, Fluorescence snapshots of PICHGFP, BLMSNAP, TRRCherry, and RPA (non-labeled) binding to a dsDNA molecule after incubation with all four proteins in the same channel. e, Schematic representation of the data in d (BLM, blue; TRR, red; PICH, green)
Supplementary Figure 3 Effect of PICH and its catalytic activity on dsDNA decatenation by the BLM, TopoIIIα, and RPA proteins.
a, Schematic representation of the creation of the single dsDNA catenane. Blue rectangles denote the recombination sites for the Tn3 resolvase. b, A magnified view of the DNA topology at the junction. c, Southern blotting of an agarose gel of reactions to show the effect of PICHWT or catalytically dead PICHK128A on the kinetics of decatenation of the single-catenane substrate by the BLM, TRR, and RPA proteins, as indicated above the lanes. Lanes 1 and 2 contain markers for the circular covalently closed and linear products, respectively; lane 3 contains substrate alone. Note that the probe allows the visualization of one of the circular molecules (green). Reactions contained 5 nM BLM, 1.25 nM TRR, 5 nM RPA, and 10 nM PICHWT or PICHK128A. d, Quantification of the combined data from c and additional experiments. Data shown are means and s.e.m. from n = 3 independent experiments. The reactions were approximated by a single-exponential decay. Parameters for data fitting are listed in Supplementary Table 2
a, Fluorescence snapshots and schematic representation (BLM, blue; TRR, red; PICH, green) of BLMSNAP and TRRCherry binding to a PICH-coated dsDNA (same molecule as shown in Fig. 2b). b, Normalized fluorescence intensities of BLMSNAP and TRRCherry along the PICH-coated dsDNA shown in a; the very similar patterns indicate strong colocalization, which indicates that BLM and TRR bind as a single complex. c, Fluorescence snapshots and schematic representation (BLM, blue; TRR, red) of BLMSNAP and TRRCherry binding to dsDNA at low coverage. The strong colocalization again demonstrates that BLM and TRR bind as a tight complex. d, Normalized fluorescence intensities of BLMSNAP and TRRCherry along the PICH-coated dsDNA stretch shown in c; the very similar patterns indicate that BLM and TRR bind as a single complex. e, Immunofluorescence image of a UFB coated by PICH (green), RMI1 (red), and BLM (blue) in an HCT116 cell line where TopoIIIα was not degraded. Scale bar, 1 μm. f, Immunofluorescence image of an RMI1-negative (red) UFB coated by PICH (green) and BLM (blue) in an HCT116 cell line where TopoIIIα was degraded before mitosis. Scale bar, 1 μm. g, Western blot analysis of TopoIIIα before and after auxin-induced degradation in mitosis. Phospho-histone H3 was used as a loading control
Supplementary Figure 5 RPA excludes BLM and TRR from ssDNA, which instead are recruited to PICH-coated dsDNA.
a, Immunofluorescence images of an fsUFB visualized by staining for PICH (green) and for the FANCD2 protein (red), which marks the termini of fsUFBs. Scale bar, 2 μm. b, Fluorescence snapshots of BLMSNAP, TRRCherry, and RPA (non-labeled) binding to a single- and double-stranded DNA hybrid molecule before (1) and after (3) coating with PICHGFP (2). c, Schematic representation of the naked single-stranded and double-stranded DNA molecule (0) and the DNA-bound proteins from b (1–3) (BLM, blue; TRR, red; RPA, white; PICH, green). d, Fluorescence snapshots of the recruitment of BLMSNAP and TRRCherry to PICHGFP-coated dsDNA and naked ssDNA in the absence of RPA. e, Schematic representation of the data from d (BLM, blue; TRR, red; PICH, green)
a, Schematic representation of the workflow for LRI construction. See the Methods for further details. b, Enlarged image of the DNA structure at the interlinked section of the LRI molecule, representing two converging replication forks. c, Agarose gel analysis of the plasmids used to construct the LRI substrate before and after creation of ssDNA gaps by restriction digestion. Note that the SpeI site is not recognized because it is located within the gapped single-stranded region. d, Agarose gel analysis of the annealed heterodimer DNA circles (left) and the linked LRI (right) by restriction digestion. Note that the SpeI site is restored by linking of the two DNAs
Supplementary Figure 7 The BTRR disentangles the LRI efficiently and PICH modestly stimulates this activity.
a, Agarose gel of the time course of LRI disjunction by either BLM and TRR (left) or BLM, TRR, and RPA (right). Lane 1 contains the circular and linear product markers; lane 2 contains the substrate only. Reactions contained 20 nM BLM, 5 nM TRR, and 30 nM RPA. b, Polyacrylamide gel of the time course of double–Holliday junction (dHJ) dissolution by either BLM and TRR alone (left) or BLM, TRR, and RPA (right). Reactions contained 20 nM BLM, 5 nM TRR, and 30 nM RPA. c, Quantification of the combined data from a and b and additional experiments. Note that the molar amounts of substrates and enzymes were equal in the two reactions. The reactions were approximated by a single-exponential decay. Parameters for data fitting are listed in Supplementary Table 2. Data shown are means and s.e.m. from n = 3 independent experiments. d, Agarose gel of the time course of LRI disjunction by the BTRR in the absence and presence of either PICHWT or PICHK128A, as indicated above the lanes. Lane 1 contains the circular and linear product markers; lane 2 contains the substrate only. Fast-migrating bands are single-stranded products resulting from unwinding of the whole plasmid by BLM at long incubation times. Reactions contained 20 nM BLM, 5 nM TRR, 30 nM RPA, and 20 nM PICHWT or PICHK128A. e, Quantification of the combined data from d and additional experiments. Data shown are means and s.e.m. from n = 3 independent experiments. The reactions were approximated by a single-exponential decay. Parameters for data fitting are listed in Supplementary Table 2
a, Comparison of the effect of RPAWT and a DNA-binding-deficient mutant, RPA6DBD, on LRI disjunction by the BLM and TRR proteins analyzed on an agarose gel. Lane 1 contains the circular and linear product markers; lane 2 contains the substrate only. Fast-migrating bands are single-stranded products resulting from unwinding of the whole plasmid by BLM at high RPA concentrations. Reactions contained 20 nM BLM, 5 nM TRR, and indicated concentrations of RPAWT or RPA6DBD. b, RPA6DBD still binds to TRR, as shown by mCherry pulldown of RPA by TRRCherry. Protein concentrations were as follows: 100 nM RPAWT or RPA6DBD, 200 nM TRRCherry. c, The ssDNA affinity of RPA6DBD is reduced by at least two orders of magnitude compared to wild-type protein, as shown by a mobility shift assay on a polyacrylamide gel. Lane 1 depicts the ssDNA substrate in the absence of RPA. d, In contrast to RPA, E. coli SSB does not promote formation of circular products by the BLM and TRR proteins during LRI disjunction analyzed on an agarose gel. Lane 1 contains the circular and linear product markers; lane 2 contains the substrate only. Fast-migrating bands are single-stranded products resulting from unwinding of the whole plasmid by BLM at high RPA concentrations. Reactions contained 20 nM BLM, 5 nM TRR, and 10, 20, 50, or 100 nM RPA or SSB. e, Quantification of the combined data from d and two additional experiments (dark gray bars, circular DNA; black bars, linear DNA; light gray bars, the ssDNA product from unwinding of the whole plasmid by BLM supported by TRR and RPA). Data shown are means and s.e.m. of n = 3 independent experiments
a, Force-extension curve of partial single-stranded and double-stranded DNA molecules incubated with BTRR (red) or BTRR and RPA (green); the curves correspond to the same molecules displayed in b. The arrow indicates ssDNA rupture due to breakage of the weaker (non-covalent) TRR–DNA bond at a force below the DNA overstretching transition. b, Representative fluorescence snapshots of BTRR (red) binding on a single-stranded and double-stranded DNA hybrid molecule, in the absence (top) or presence (bottom) of RPA (green). Note the exclusion of BTRR from the ssDNA in the latter case
PICH (light green) recruits the BTRR (red triangle) to the double-stranded section of the UFBs, while RPA (orange) excludes the BTRR from any single-stranded stretches. fsUFBs, marked by FANCD2 foci at their termini (light blue circles), frequently contain ssDNA. The majority of fsUFBs are unlinked by the BTRR, where RPA prevents detrimental UFB breakage by negatively regulating the binding of BLM and TRR to ssDNA. Centromeric UFBs are almost exclusively double-stranded and are marked by CENPA foci (black circles) at their termini. BLM and TRR can substitute for TopoIIα in the decatenation of cUFBs in rare cases where the decatenase activity of TopoIIα is limiting
Supplementary Figures 1–10, Supplementary Tables 1 and 2, and Supplementary Notes 1 and 2
About this article
Cite this article
Sarlós, K., Biebricher, A.S., Bizard, A.H. et al. Reconstitution of anaphase DNA bridge recognition and disjunction. Nat Struct Mol Biol 25, 868–876 (2018). https://doi.org/10.1038/s41594-018-0123-8
Current Opinion in Genetics & Development (2020)
Biochemical Journal (2020)
Histone H2A phosphorylation recruits topoisomerase II α to centromeres to safeguard genomic stability
The EMBO Journal (2020)
Journal of Biological Chemistry (2020)
Nature Structural & Molecular Biology (2019)