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Centrosomes are multifunctional regulators of genome stability

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Abstract

The maintenance of genome stability is critical for proper cell function, and loss of this stability contributes to many human diseases and developmental disorders. Therefore, cells have evolved partially redundant mechanisms to monitor and protect the genome. One subcellular organelle implicated in the maintenance of genome stability is the centrosome, best known as the primary microtubule organizing center of most animal cells. Centrosomes serve many different roles throughout the cell cycle, and many of those roles, including mitotic spindle assembly, nucleation of the interphase microtubule array, DNA damage response, and efficient cell cycle progression, have been proposed to help maintain genome stability. As a result, the centrosome is itself a highly regulated entity. Here, we review evidence concerning the significance of the centrosome in promoting genome integrity. Recent advances permitting acute and persistent centrosome removal suggest we still have much to learn regarding the specific function and actual importance of centrosomes in different contexts, as well as how cells may compensate for centrosome dysfunction to maintain the integrity of the genome. Although many animal cells survive and proliferate in the absence of centrosomes, they do so aberrantly. Based on these and other studies, we conclude that centrosomes serve as critical, multifunctional organelles that promote genome stability.

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Abbreviations

CIN:

Chromosomal instability

MT:

Microtubule

MTOC:

Microtubule organizing center

aMTOC:

Acentriolar microtubule organizing center

PCM:

Pericentriolar material

RNAi:

RNA interference

NEB:

Nuclear envelope breakdown

SAC:

Spindle assembly checkpoint

NSC:

Neural stem cell

mGSC:

Male germline stem cell

References

  • Abraham RT (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 15:2177–2196

    Article  CAS  PubMed  Google Scholar 

  • Arquint C, Gabryjonczyk AM, Nigg EA (2014) Centrosomes as signalling centres. Philos Trans R Soc Lond B Biol Sci 369:20130464

    Article  PubMed Central  PubMed  Google Scholar 

  • Basto R, Lau J, Vinogradova T, Gardiol A, Woods CG, Khodjakov A, Raff JW (2006) Flies without centrioles. Cell 125:1375–1386

    Article  CAS  PubMed  Google Scholar 

  • Baumbach J, Novak ZA, Raff JW, Wainman A (2015) Dissecting the function and assembly of acentriolar microtubule organizing centers in Drosophila cells in vivo. PLoS Genet 11:e1005261

    Article  PubMed Central  PubMed  Google Scholar 

  • Bazzi H, Anderson KV (2014) Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo. Proc Natl Acad Sci U S A 111:E1491–E1500

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Blachon S, Gopalakrishnan J, Omori Y, Polyanovsky A, Church A, Nicastro D, Malicki J, Avidor-Reiss T (2008) Drosophila asterless and vertebrate Cep152 are orthologs essential for centriole duplication. Genetics 180:2081–2094

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bolgioni AF, Ganem NJ (2015) The interplay between centrosomes and the hippo tumor suppressor pathway. Chromosome Res doi:10.1007/s10577-015-9502-8

  • Bonaccorsi S, Giansanti MG, Gatti M (1998) Spindle self-organization and cytokinesis during male meiosis in asterless mutants of Drosophila melanogaster. J Cell Biol 142:751–761

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Borel F, Lohez OD, Lacroix FB, Margolis RL (2002) Multiple centrosomes arise from tetraploidy checkpoint failure and mitotic centrosome clusters in p53 and RB pocket protein-compromised cells. Proc Natl Acad Sci U S A 99:9819–9824

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Brito DA, Rieder CL (2006) Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint. Curr Biol 16:1194–1200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Brito DA, Yang Z, Rieder CL (2008) Microtubules do not promote mitotic slippage when the spindle assembly checkpoint cannot be satisfied. J Cell Biol 182:623–629

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Buffin E, Emre D, Karess RE (2007) Flies without a spindle checkpoint. Nat Cell Biol 9:565–572

    Article  CAS  PubMed  Google Scholar 

  • Canman JC, Cameron LA, Maddox PS, Straight A, Tirnauer JS, Mitchison TJ, Fang G, Kapoor TM, Salmon ED (2003) Determining the position of the cell division plane. Nature 424:1074–1078

    Article  CAS  PubMed  Google Scholar 

  • Castellanos E, Dominguez P, Gonzalez C (2008) Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability. Curr Biol 18:1209–1214

    Article  CAS  PubMed  Google Scholar 

  • Cimini D, Howell B, Maddox P, Khodjakov A, Degrassi F, Salmon ED (2001) Merotelic kinetochore orientation is a major mechanism of aneuploidy in mitotic mammalian tissue cells. J Cell Biol 153:517–527

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cosenza MR, Krämer A (2015) Centrosome amplification, chromosomal instability and cancer: mechanistic, clinical and therapeutic issues. Chromosome Res. In press

  • Crasta K, Ganem NJ, Dagher R, Lantermann AB, Ivanova EV, Pan Y, Nezi L, Protopopov A, Chowdhury D, Pellman D (2012) DNA breaks and chromosome pulverization from errors in mitosis. Nature 482:53–58

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dekanty A, Barrio L, Muzzopappa M, Auer H, Milan M (2012) Aneuploidy-induced delaminating cells drive tumorigenesis in Drosophila epithelia. Proc Natl Acad Sci U S A 109:20549–20554

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Doxsey S, McCollum D, Theurkauf W (2005) Centrosomes in cellular regulation. Annu Rev Cell Dev Biol 21:411–434

    Article  CAS  PubMed  Google Scholar 

  • Feldman JL, Priess JR (2012) A role for the centrosome and PAR-3 in the hand-off of MTOC function during epithelial polarization. Curr Biol 22:575–582

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Foley EA, Kapoor TM (2013) Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore. Nat Rev Mol Cell Biol 14:25–37

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fox DT, Gall JG, Spradling AC (2010) Error-prone polyploid mitosis during normal Drosophila development. Genes Dev 24:2294–2302

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fukasawa K (2007) Oncogenes and tumour suppressors take on centrosomes. Nat Rev Cancer 7:911–924

    Article  CAS  PubMed  Google Scholar 

  • Goshima G, Mayer M, Zhang N, Stuurman N, Vale RD (2008) Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle. J Cell Biol 181:421–429

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Green RA, Paluch E, Oegema K (2012) Cytokinesis in animal cells. Annu Rev Cell Dev Biol 28:29–58

    Article  CAS  PubMed  Google Scholar 

  • Hamill DR, Severson AF, Carter JC, Bowerman B (2002) Centrosome maturation and mitotic spindle assembly in C. elegans require SPD-5, a protein with multiple coiled-coil domains. Dev Cell 3:673–684

    Article  CAS  PubMed  Google Scholar 

  • Harris TJ, Peifer M (2007) aPKC controls microtubule organization to balance adherens junction symmetry and planar polarity during development. Dev Cell 12:727–738

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hashimoto T (2013) A ring for all: gamma-tubulin-containing nucleation complexes in acentrosomal plant microtubule arrays. Curr Opin Plant Biol 16:698–703

    Article  CAS  PubMed  Google Scholar 

  • Hayward D, Metz J, Pellacani C, Wakefield JG (2014) Synergy between multiple microtubule-generating pathways confers robustness to centrosome-driven mitotic spindle formation. Dev Cell 28:81–93

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Heald R, Tournebize R, Blank T, Sandaltzopoulos R, Becker P, Hyman A, Karsenti E (1996) Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. Nature 382:420–425

    Article  CAS  PubMed  Google Scholar 

  • Heinrichs A (2007) A centrosome-integrity checkpoint. Nat Rev Mol Cell Biol 8:98

    Article  CAS  Google Scholar 

  • Hinchcliffe EH, Miller FJ, Cham M, Khodjakov A, Sluder G (2001) Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science 291:1547–1550

    Article  CAS  PubMed  Google Scholar 

  • Holland AJ, Cleveland DW (2009) Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis. Nat Rev Mol Cell Biol 10:478–487

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hornick JE, Mader CC, Tribble EK, Bagne CC, Vaughan KT, Shaw SL, Hinchcliffe EH (2011) Amphiastral mitotic spindle assembly in vertebrate cells lacking centrosomes. Curr Biol 21:598–605

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hut HM, Lemstra W, Blaauw EH, Van Cappellen GW, Kampinga HH, Sibon OC (2003) Centrosomes split in the presence of impaired DNA integrity during mitosis. Mol Biol Cell 14:1993–2004

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Inanc B, Dodson H, Morrison CG (2010) A centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in G2 phase after DNA damage. Mol Biol Cell 21:3866–3877

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Insolera R, Bazzi H, Shao W, Anderson KV, Shi SH (2014) Cortical neurogenesis in the absence of centrioles. Nat Neurosci 17:1528–1535

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Janssen A, van der Burg M, Szuhai K, Kops GJ, Medema RH (2011) Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations. Science 333:1895–1898

    Article  CAS  PubMed  Google Scholar 

  • Januschke J, Llamazares S, Reina J, Gonzalez C (2011) Drosophila neuroblasts retain the daughter centrosome. Nat Commun 2:243

    Article  PubMed Central  PubMed  Google Scholar 

  • Januschke J, Reina J, Llamazares S, Bertran T, Rossi F, Roig J, Gonzalez C (2013) Centrobin controls mother-daughter centriole asymmetry in Drosophila neuroblasts. Nat Cell Biol 15:241–248

    Article  CAS  PubMed  Google Scholar 

  • Kapoor TM, Mayer TU, Coughlin ML, Mitchison TJ (2000) Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J Cell Biol 150:975–988

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kaseda K, McAinsh AD, Cross RA (2012) Dual pathway spindle assembly increases both the speed and the fidelity of mitosis. Biol Open 1:12–18

    Article  PubMed Central  PubMed  Google Scholar 

  • Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51:6304–6311

    CAS  PubMed  Google Scholar 

  • Khodjakov A, Rieder CL (1999) The sudden recruitment of gamma-tubulin to the centrosome at the onset of mitosis and its dynamic exchange throughout the cell cycle, do not require microtubules. J Cell Biol 146:585–596

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Khodjakov A, Rieder CL (2001) Centrosomes enhance the fidelity of cytokinesis in vertebrates and are required for cell cycle progression. J Cell Biol 153:237–242

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Khodjakov A, Cole RW, Oakley BR, Rieder CL (2000) Centrosome-independent mitotic spindle formation in vertebrates. Curr Biol 10:59–67

    Article  CAS  PubMed  Google Scholar 

  • Lambrus BG, Uetake Y, Clutario KM, Daggubati V, Snyder M, Sluder G, Holland AJ (2015) p53 protects against genome instability following centriole duplication failure. J Cell Biol 210:63–77

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lavia P (2015) The GTPase RAN regulates multiple steps of the centrosome life cycle. Chromosome Res. in press

  • Lecland N, Debec A, Delmas A, Moutinho-Pereira S, Malmanche N, Bouissou A, Dupre C, Jourdan A, Raynaud-Messina B, Maiato H et al (2013) Establishment and mitotic characterization of new Drosophila acentriolar cell lines from DSas-4 mutant. Biol Open 2:314–323

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lerit DA, Rusan NM (2013) PLP inhibits the activity of interphase centrosomes to ensure their proper segregation in stem cells. J Cell Biol 202:1013–1022

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lerit DA, Jordan HA, Poulton JS, Fagerstrom CJ, Galletta BJ, Peifer M, Rusan NM (2015) Interphase centrosome organization by the PLP-Cnn scaffold is required for centrosome function. J Cell Biol 210:79–97

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Li K, Xu EY, Cecil JK, Turner FR, Megraw TL, Kaufman TC (1998) Drosophila centrosomin protein is required for male meiosis and assembly of the flagellar axoneme. J Cell Biol 141:455–467

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Loffler H, Fechter A, Liu FY, Poppelreuther S, Kramer A (2013) DNA damage-induced centrosome amplification occurs via excessive formation of centriolar satellites. Oncogene 32:2963–2972

    Article  CAS  PubMed  Google Scholar 

  • Meads T, Schroer TA (1995) Polarity and nucleation of microtubules in polarized epithelial cells. Cell Motil Cytoskeleton 32:273–288

    Article  CAS  PubMed  Google Scholar 

  • Megraw TL, Li K, Kao LR, Kaufman TC (1999) The centrosomin protein is required for centrosome assembly and function during cleavage in Drosophila. Development 126:2829–2839

    CAS  PubMed  Google Scholar 

  • Megraw TL, Kao LR, Kaufman TC (2001) Zygotic development without functional mitotic centrosomes. Curr Biol 11:116–120

    Article  CAS  PubMed  Google Scholar 

  • Mikule K, Delaval B, Kaldis P, Jurcyzk A, Hergert P, Doxsey S (2007) Loss of centrosome integrity induces p38-p53-p21-dependent G1-S arrest. Nat Cell Biol 9:160–170

    Article  CAS  PubMed  Google Scholar 

  • Mullee LI, Morrison CG (2015) Centrosomes in the DNA damage response – the hub outside the centre. Chromosome Res doi:10.1007/s10577-015-9503-7

  • Musacchio A, Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8:379–393

    Article  CAS  PubMed  Google Scholar 

  • Nam HJ, van Deursen JM (2014) Cyclin B2 and p53 control proper timing of centrosome separation. Nat Cell Biol 16:538–549

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nam HJ, Naylor RM, van Deursen JM (2015) Centrosome dynamics as a source of chromosomal instability. Trends Cell Biol 25:65–73

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nano M, Basto R (2015) The Janus soul of centrosomes: a paradoxical role in disease? Chromosome Res. In press

  • Nigg EA, Raff JW (2009) Centrioles, centrosomes, and cilia in health and disease. Cell 139:663–678

    Article  CAS  PubMed  Google Scholar 

  • Nigg EA, Stearns T (2011) The centrosome cycle: centriole biogenesis, duplication and inherent asymmetries. Nat Cell Biol 13:1154–1160

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Palazzo RE, Vogel JM, Schnackenberg BJ, Hull DR, Wu X (2000) Centrosome maturation. Curr Top Dev Biol 49:449–470

    Article  CAS  PubMed  Google Scholar 

  • Piel M, Nordberg J, Euteneuer U, Bornens M (2001) Centrosome-dependent exit of cytokinesis in animal cells. Science 291:1550–1553

    Article  CAS  PubMed  Google Scholar 

  • Poulton JS, Mu FW, Roberts DM, Peifer M (2013) APC2 and Axin promote mitotic fidelity by facilitating centrosome separation and cytoskeletal regulation. Development 140:4226–4236

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Poulton JS, Cuningham JC, Peifer M (2014) Acentrosomal Drosophila epithelial cells exhibit abnormal cell division, leading to cell death and compensatory proliferation. Dev Cell 30:731–745

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Prosser SL, Sahota NK, Pelletier L, Morrison CG, Fry AM (2015) Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion in mitosis. J Cell Biol 209:339–348

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rebollo E, Sampaio P, Januschke J, Llamazares S, Varmark H, Gonzalez C (2007) Functionally unequal centrosomes drive spindle orientation in asymmetrically dividing Drosophila neural stem cells. Dev Cell 12:467–474

    Article  CAS  PubMed  Google Scholar 

  • Rieder CL, Maiato H (2004) Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint. Dev Cell 7:637–651

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues-Martins A, Riparbelli M, Callaini G, Glover DM, Bettencourt-Dias M (2008) From centriole biogenesis to cellular function: centrioles are essential for cell division at critical developmental stages. Cell Cycle 7:11–16

    Article  CAS  PubMed  Google Scholar 

  • Rusan NM, Peifer M (2007) A role for a novel centrosome cycle in asymmetric cell division. J Cell Biol 177:13–20

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sakurai H, Okado M, Ito F, Kawasaki K (2011) Anaphase DNA bridges induced by lack of RecQ5 in Drosophila syncytial embryos. FEBS Lett 585:1923–1928

    Article  CAS  PubMed  Google Scholar 

  • Schmutz C, Spang A (2005) Knockdown of the centrosomal component SAS-5 results in defects in nuclear morphology in Caenorhabditis elegans. Eur J Cell Biol 84:75–82

    Article  CAS  PubMed  Google Scholar 

  • Schoenfelder KP, Montague RA, Paramore SV, Lennox AL, Mahowald AP, Fox DT (2014) Indispensable pre-mitotic endocycles promote aneuploidy in the Drosophila rectum. Development 141:3551–3560

    Article  CAS  PubMed  Google Scholar 

  • Schumacher JM, Ashcroft N, Donovan PJ, Golden A (1998) A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos. Development 125:4391–4402

    CAS  PubMed  Google Scholar 

  • Sibon OC, Kelkar A, Lemstra W, Theurkauf WE (2000) DNA-replication/DNA-damage-dependent centrosome inactivation in Drosophila embryos. Nat Cell Biol 2:90–95

    Article  CAS  PubMed  Google Scholar 

  • Silkworth WT, Nardi IK, Paul R, Mogilner A, Cimini D (2012) Timing of centrosome separation is important for accurate chromosome segregation. Mol Biol Cell 23:401–411

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Singh P, Ramdas Nair A, Cabernard C (2014) The centriolar protein Bld10/Cep135 is required to establish centrosome asymmetry in Drosophila neuroblasts. Curr Biol 24:1548–1555

    Article  CAS  PubMed  Google Scholar 

  • Sir JH, Putz M, Daly O, Morrison CG, Dunning M, Kilmartin JV, Gergely F (2013) Loss of centrioles causes chromosomal instability in vertebrate somatic cells. J Cell Biol 203:747–756

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Srsen V, Gnadt N, Dammermann A, Merdes A (2006) Inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle. J Cell Biol 174:625–630

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stevens NR, Raposo AA, Basto R, St Johnston D, Raff JW (2007) From stem cell to embryo without centrioles. Curr Biol 17:1498–1503

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sunkel CE, Glover DM (1988) polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J Cell Sci 89(Pt 1):25–38

    PubMed  Google Scholar 

  • Takada S, Kelkar A, Theurkauf WE (2003) Drosophila checkpoint kinase 2 couples centrosome function and spindle assembly to genomic integrity. Cell 113:87–99

    Article  CAS  PubMed  Google Scholar 

  • Tanenbaum ME, Medema RH (2010) Mechanisms of centrosome separation and bipolar spindle assembly. Dev Cell 19:797–806

    Article  CAS  PubMed  Google Scholar 

  • Uetake Y, Loncarek J, Nordberg JJ, English CN, La Terra S, Khodjakov A, Sluder G (2007) Cell cycle progression and de novo centriole assembly after centrosomal removal in untransformed human cells. J Cell Biol 176:173–182

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ulrich E, Boehmelt G, Bird A, Beug H (1992) Immortalization of conditionally transformed chicken cells: loss of normal p53 expression is an early step that is independent of cell transformation. Genes Dev 6:876–887

    Article  CAS  PubMed  Google Scholar 

  • Vaizel-Ohayon D, Schejter ED (1999) Mutations in centrosomin reveal requirements for centrosomal function during early Drosophila embryogenesis. Curr Biol 9:889–898

    Article  CAS  PubMed  Google Scholar 

  • Varmark H, Llamazares S, Rebollo E, Lange B, Reina J, Schwarz H, Gonzalez C (2007) Asterless is a centriolar protein required for centrosome function and embryo development in Drosophila. Curr Biol 17:1735–1745

    Article  CAS  PubMed  Google Scholar 

  • Wainman A, Buster DW, Duncan T, Metz J, Ma A, Sharp D, Wakefield JG (2009) A new Augmin subunit, Msd1, demonstrates the importance of mitotic spindle-templated microtubule nucleation in the absence of functioning centrosomes. Genes Dev 23:1876–1881

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wong YL, Anzola JV, Davis RL, Yoon M, Motamedi A, Kroll A, Seo CP, Hsia JE, Kim SK, Mitchell JW et al (2015) Cell biology. Reversible centriole depletion with an inhibitor of Polo-like kinase 4. Science 348:1155–1160

    Article  CAS  PubMed  Google Scholar 

  • Yamashita YM, Mahowald AP, Perlin JR, Fuller MT (2007) Asymmetric inheritance of mother versus daughter centrosome in stem cell division. Science 315:518–521

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang Y, Foreman O, Wigle DA, Kosari F, Vasmatzis G, Salisbury JL, van Deursen J, Galardy PJ (2012) USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis. J Clin Invest 122:4362–4374

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang CZ, Spektor A, Cornils H, Francis JM, Jackson EK, Liu S, Meyerson M, Pellman D (2015) Chromothripsis from DNA damage in micronuclei. Nature 522:179–184

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Nasser M. Rusan, Mark Peifer, and Erich Kushner for critical comments. DAL is supported by a Lenfant Biomedical Postdoctoral Fellowship and a NHLBI Career Transition Award (1K22HL126922). JSP is supported by the Peifer lab grant NIH R01GM067236.

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    Authors and Affiliations

    1. Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute; National Institutes of Health, Bethesda, MD, 20892, USA

      Dorothy A. Lerit

    2. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA

      John S. Poulton

    3. National Institutes of Health, 50 South Drive, Building 50, Room 2122, Bethesda, MD, 20892, USA

      Dorothy A. Lerit

    4. University of North Carolina, Fordham 519, CB#3280, Chapel Hill, NC, 27599, USA

      John S. Poulton

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    Responsible Editors: Daniela Cimini and Giulia Guarguaglini

    Dorothy A. Lerit and John S. Poulton contributed equally to this work.

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    Lerit, D.A., Poulton, J.S. Centrosomes are multifunctional regulators of genome stability. Chromosome Res 24, 5–17 (2016). https://doi.org/10.1007/s10577-015-9506-4

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