The leukemia-associated Rho guanine nucleotide exchange factor LARG is required for efficient replication stress signaling

References

• Kourlas PJ, Strout MP, Becknell B, Veronese ML, Croce CM, Theil KS, Krahe R, Ruutu T, Knuutila S, Bloomfield CD, et al. Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: evidence for its fusion with MLL in acute myeloid leukemia. Proc Natl Acad Sci U S A 2000; 97:2145-50; PMID:10681437; http://dx.doi.org/10.1073/pnas.040569197
   PubMed Web of Science ®Google Scholar
• Suzuki N, Nakamura S, Mano H, Kozasa T. Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF. Proc Natl Acad Sci U S A 2003; 100:733-8; PMID:12515866; http://dx.doi.org/10.1073/pnas.0234057100
   PubMed Web of Science ®Google Scholar
• Chikumi H, Barac A, Behbahani B, Gao Y, Teramoto H, Zheng Y, Gutkind JS. Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potential. Oncogene 2004; 23:233-40; PMID:14712228; http://dx.doi.org/10.1038/sj.onc.1207012
   PubMed Web of Science ®Google Scholar
• Mikelis CM, Palmby TR, Simaan M, Li W, Szabo R, Lyons R, Martin D, Yagi H, Fukuhara S, Chikumi H, et al. PDZ-RhoGEF and LARG are essential for embryonic development and provide a link between thrombin and LPA receptors and Rho activation. J Biol Chem 2013; 288:12232-43; PMID:23467409; http://dx.doi.org/10.1074/jbc.M112.428599
   PubMed Web of Science ®Google Scholar
• Ong DC, Ho YM, Rudduck C, Chin K, Kuo WL, Lie DK, Chua CL, Tan PH, Eu KW, Seow-Choen F, et al. LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast and colorectal cancer. Oncogene 2009; 28:4189-200; PMID:19734946; http://dx.doi.org/10.1038/onc.2009.266
   PubMed Web of Science ®Google Scholar
• Horiuchi A, Imai T, Wang C, Ohira S, Feng Y, Nikaido T, Konishi I. Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma. Lab Invest 2003; 83:861-70; PMID:12808121; http://dx.doi.org/10.1097/01.LAB.0000073128.16098.31
   PubMed Web of Science ®Google Scholar
• Kamai T, Yamanishi T, Shirataki H, Takagi K, Asami H, Ito Y, Yoshida K. Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer. Clin Cancer Res 2004; 10:4799-805; PMID:15269155; http://dx.doi.org/10.1158/1078-0432.CCR-0436-03
   PubMed Web of Science ®Google Scholar
• Pan Y, Bi F, Liu N, Xue Y, Yao X, Zheng Y, Fan D. Expression of seven main Rho family members in gastric carcinoma. Biochem Biophys Res Commun 2004; 315:686-91; PMID:14975755; http://dx.doi.org/10.1016/j.bbrc.2004.01.108
   PubMed Web of Science ®Google Scholar
• Li XR, Ji F, Ouyang J, Wu W, Qian LY, Yang KY. Overexpression of RhoA is associated with poor prognosis in hepatocellular carcinoma. Eur J Sur Oncol 2006; 32:1130-4; PMID:16806792; http://dx.doi.org/10.1016/j.ejso.2006.05.012
   PubMed Web of Science ®Google Scholar
• Reuther GW, Lambert QT, Booden MA, Wennerberg K, Becknell B, Marcucci G, Sondek J, Caligiuri MA, Der CJ. Leukemia-associated Rho guanine nucleotide exchange factor, a Dbl family protein found mutated in leukemia, causes transformation by activation of RhoA. J Biol Chem 2001; 276:27145-51; PMID:11373293; http://dx.doi.org/10.1074/jbc.M103565200
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646-74; PMID:21376230; http://dx.doi.org/10.1016/j.cell.2011.02.013
   PubMed Web of Science ®Google Scholar
• Collis SJ, Barber LJ, Clark AJ, Martin JS, Ward JD, Boulton SJ. HCLK2 is essential for the mammalian S-phase checkpoint and impacts on Chk1 stability. Nat Cell Biol 2007; 9:391-401; PMID:17384638; http://dx.doi.org/10.1038/ncb1555
   PubMed Web of Science ®Google Scholar
• Horejsi Z, Takai H, Adelman CA, Collis SJ, Flynn H, Maslen S, Skehel JM, de Lange T, Boulton SJ. CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability. Mol Cell 2010; 39:839-50; PMID:20864032; http://dx.doi.org/10.1016/j.molcel.2010.08.037
   PubMed Web of Science ®Google Scholar
• Takai H, Wang RC, Takai KK, Yang H, de Lange T. Tel2 regulates the stability of PI3K-related protein kinases. Cell 2007; 131:1248-59; PMID:18160036; http://dx.doi.org/10.1016/j.cell.2007.10.052
   PubMed Web of Science ®Google Scholar
• Dubash AD, Guilluy C, Srougi MC, Boulter E, Burridge K, Garcia-Mata R. The small GTPase RhoA localizes to the nucleus and is activated by Net1 and DNA damage signals. PLoS One 2011; 6:e17380; PMID:21390328; http://dx.doi.org/10.1371/journal.pone.0017380
   PubMed Web of Science ®Google Scholar
• Goulimari P, Knieling H, Engel U, Grosse R. LARG and mDia1 link Galpha12/13 to cell polarity and microtubule dynamics. Mol Biol Cell 2008; 19:30-40; PMID:17959834; http://dx.doi.org/10.1091/mbc.E06-11-1045
   PubMed Web of Science ®Google Scholar
• Griffith E, Walker S, Martin CA, Vagnarelli P, Stiff T, Vernay B, Al Sanna N, Saggar A, Hamel B, Earnshaw WC, et al. Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling. Nat Genet 2008; 40:232-6; PMID:18157127; http://dx.doi.org/10.1038/ng.2007.80
   PubMed Web of Science ®Google Scholar
• Rauch A, Thiel CT, Schindler D, Wick U, Crow YJ, Ekici AB, van Essen AJ, Goecke TO, Al-Gazali L, Chrzanowska KH, et al. Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. Science 2008; 319:816-9; PMID:18174396; http://dx.doi.org/10.1126/science.1151174
   PubMed Web of Science ®Google Scholar
• Willems M, Genevieve D, Borck G, Baumann C, Baujat G, Bieth E, Edery P, Farra C, Gerard M, Heron D, et al. Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families. J Med Genet 2010; 47:797-802; PMID:19643772; http://dx.doi.org/10.1136/jmg.2009.067298
   PubMed Web of Science ®Google Scholar
• Aoki T, Ueda S, Kataoka T, Satoh T. Regulation of mitotic spindle formation by the RhoA guanine nucleotide exchange factor ARHGEF10. BMC Cell Biol 2009; 10:56; PMID:19635168; http://dx.doi.org/10.1186/1471-2121-10-56
   PubMed Web of Science ®Google Scholar
• Collis SJ, Ciccia A, Deans AJ, Horejsi Z, Martin JS, Maslen SL, Skehel JM, Elledge SJ, West SC, Boulton SJ. FANCM and FAAP24 function in ATR-mediated checkpoint signaling independently of the Fanconi anemia core complex. Molecular cell 2008; 32:313-24; PMID:18995830; http://dx.doi.org/10.1016/j.molcel.2008.10.014
   PubMed Web of Science ®Google Scholar
• Matsuo K, Nishimura T, Hayakawa A, Ono Y, Takahashi M. Involvement of a centrosomal protein kendrin in the maintenance of centrosome cohesion by modulating Nek2A kinase activity. Biochem Biophys Res Commun 2010; 398:217-23; PMID:20599736; http://dx.doi.org/10.1016/j.bbrc.2010.06.063
   PubMed Web of Science ®Google Scholar
• Gillingham AK, Munro S. The PACT domain, a conserved centrosomal targeting motif in the coiled-coil proteins AKAP450 and pericentrin. EMBO Rep 2000; 1:524-9; PMID:11263498; http://dx.doi.org/10.1093/embo-reports/kvd105
   PubMed Web of Science ®Google Scholar
• Alderton GK, Joenje H, Varon R, Borglum AD, Jeggo PA, O'Driscoll M. Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway. Hum Mol Genet 2004; 13:3127-38; PMID:15496423; http://dx.doi.org/10.1093/hmg/ddh335
   PubMed Web of Science ®Google Scholar
• Staples CJ, Myers KN, Beveridge RD, Patil AA, Lee AJ, Swanton C, Howell M, Boulton SJ, Collis SJ. The centriolar satellite protein Cep131 is important for genome stability. J Cell Sci 2012; 125:4770-9; PMID:22797915; http://dx.doi.org/10.1242/jcs.104059
   PubMed Web of Science ®Google Scholar
• Ward IM, Chen J. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem 2001; 276:47759-62; PMID:11673449; http://dx.doi.org/10.1074/jbc.M009785200
   PubMed Web of Science ®Google Scholar
• Block WD, Yu Y, Lees-Miller SP. Phosphatidyl inositol 3-kinase-like serine/threonine protein kinases (PIKKs) are required for DNA damage-induced phosphorylation of the 32 kDa subunit of replication protein A at threonine 21. Nucleic Acids Res 2004; 32:997-1005; PMID:14872059; http://dx.doi.org/10.1093/nar/gkh265
   PubMed Web of Science ®Google Scholar
• Zou L, Elledge SJ. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 2003; 300:1542-8; PMID:12791985; http://dx.doi.org/10.1126/science.1083430
   PubMed Web of Science ®Google Scholar
• Zeman MK, Cimprich KA. Causes and consequences of replication stress. Nat Cell Biol 2014; 16:2-9; PMID:24366029; http://dx.doi.org/10.1038/ncb2897
   PubMed Web of Science ®Google Scholar
• Kitzing TM, Sahadevan AS, Brandt DT, Knieling H, Hannemann S, Fackler OT, Grosshans J, Grosse R. Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion. Genes Dev 2007; 21:1478-83; PMID:17575049; http://dx.doi.org/10.1101/gad.424807
   PubMed Web of Science ®Google Scholar
• O'Driscoll M, Ruiz-Perez VL, Woods CG, Jeggo PA, Goodship JA. A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat Genet 2003; 33:497-501; PMID:12640452; http://dx.doi.org/10.1038/ng1129
   PubMed Web of Science ®Google Scholar
• Kalay E, Yigit G, Aslan Y, Brown KE, Pohl E, Bicknell LS, Kayserili H, Li Y, Tuysuz B, Nurnberg G, et al. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat Genet 2011; 43:23-6; PMID:21131973; http://dx.doi.org/10.1038/ng.725
   PubMed Web of Science ®Google Scholar
• Sivasubramaniam S, Sun X, Pan YR, Wang S, Lee EY. Cep164 is a mediator protein required for the maintenance of genomic stability through modulation of MDC1, RPA, and CHK1. Genes Dev 2008; 22:587-600; PMID:18283122; http://dx.doi.org/10.1101/gad.1627708
   PubMed Web of Science ®Google Scholar
• Staples CJ, Myers KN, Beveridge RD, Patil AA, Howard AE, Barone G, Lee AJ, Swanton C, Howell M, Maslen S, et al. Ccdc13; a novel human centriolar satellite protein required for ciliogenesis and genome stability. J Cell Sci 2014; 127(Pt 13):2910-9; PMID:24816561; http://dx.doi.org/10.1242/jcs.147785
   PubMed Web of Science ®Google Scholar
• Alderton GK, Galbiati L, Griffith E, Surinya KH, Neitzel H, Jackson AP, Jeggo PA, O'Driscoll M. Regulation of mitotic entry by microcephalin and its overlap with ATR signalling. Nat Cell Biol 2006; 8:725-33; PMID:16783362; http://dx.doi.org/10.1038/ncb1431
   PubMed Web of Science ®Google Scholar
• Godinho SA, Picone R, Burute M, Dagher R, Su Y, Leung CT, Polyak K, Brugge JS, Thery M, Pellman D. Oncogene-like induction of cellular invasion from centrosome amplification. Nature 2014; 510:167-71; PMID:24739973; http://dx.doi.org/10.1038/nature13277
   PubMed Web of Science ®Google Scholar
• Chaki M, Airik R, Ghosh AK, Giles RH, Chen R, Slaats GG, Wang H, Hurd TW, Zhou W, Cluckey A, et al. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell 2012; 150:533-48; PMID:22863007; http://dx.doi.org/10.1016/j.cell.2012.06.028
   PubMed Web of Science ®Google Scholar
• Choi HJ, Lin JR, Vannier JB, Slaats GG, Kile AC, Paulsen RD, Manning DK, Beier DR, Giles RH, Boulton SJ, et al. NEK8 Links the ATR-Regulated Replication Stress Response and S Phase CDK Activity to Renal Ciliopathies. Mol Cell 2013; 51:423-39; PMID:23973373; http://dx.doi.org/10.1016/j.molcel.2013.08.006
   PubMed Web of Science ®Google Scholar
• Valdes-Sanchez L, De la Cerda B, Diaz-Corrales FJ, Massalini S, Chakarova CF, Wright AF, Bhattacharya SS. ATR localizes to the photoreceptor connecting cilium and deficiency leads to severe photoreceptor degeneration in mice. Hum Mol Genet 2013; 22:1507-15; PMID:23297361; http://dx.doi.org/10.1093/hmg/dds563
   PubMedGoogle Scholar
• Zhou W, Otto EA, Cluckey A, Airik R, Hurd TW, Chaki M, Diaz K, Lach FP, Bennett GR, Gee HY, et al. FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair. Nat Genet 2012; 44:910-5; PMID:22772369; http://dx.doi.org/10.1038/ng.2347
   PubMed Web of Science ®Google Scholar
• Chavali PL, Gergely F. Cilia born out of shock and stress. Embo J 2013; 32:3011-3; PMID:24185901; http://dx.doi.org/10.1038/emboj.2013.241
   PubMed Web of Science ®Google Scholar
• Stiff T, Alagoz M, Alcantara D, Outwin E, Brunner HG, Bongers EM, O'Driscoll M, Jeggo PA. Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of Meier-Gorlin syndrome. PLoS Genet 2013; 9:e1003360; PMID:23516378; http://dx.doi.org/10.1371/journal.pgen.1003360
   PubMedGoogle Scholar
• Pan J, You Y, Huang T, Brody SL. RhoA-mediated apical actin enrichment is required for ciliogenesis and promoted by Foxj1. J Cell Sci 2007; 120:1868-76; PMID:17488776; http://dx.doi.org/10.1242/jcs.005306
   PubMed Web of Science ®Google Scholar
• Madhivanan K, Mukherjee D, Aguilar RC. Lowe syndrome: Between primary cilia assembly and Rac1-mediated membrane remodeling. Commun Integr Biol 2012; 5:641-4; PMID:23739214; http://dx.doi.org/10.4161/cib.21952
   PubMedGoogle Scholar
• Cheung HC, San Lucas FA, Hicks S, Chang K, Bertuch AA, Ribes-Zamora A. An S/T-Q cluster domain census unveils new putative targets under Tel1/Mec1 control. BMC Genomics 2012; 13:664; PMID:23176708; http://dx.doi.org/10.1186/1471-2164-13-664
   PubMed Web of Science ®Google Scholar
• Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER, 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 2007; 316:1160-6; PMID:17525332; http://dx.doi.org/10.1126/science.1140321
   PubMed Web of Science ®Google Scholar
• O'Driscoll M. Diseases associated with defective responses to DNA damage. Cold Spring Harb Perspect Biol 2012; 4:1-25; PMID:23209155; http://dx.doi.org/10.1101/cshperspect.a012773
   PubMed Web of Science ®Google Scholar
• Alcantara D, O'Driscoll M. Congenital microcephaly. Am J Med Genet C Semin Med Genet 2014; 166C(2):124-39; PMID:24816482
   PubMed Web of Science ®Google Scholar