Il lavoro di tesi si è focalizzato sulla localizzazione e sul ruolo di BRCA1 nella riparazione del DNA in seguito al trattamento con MMS. Questo ha permesso di aggiungere altre informazioni per ampliare le conoscenze sul coinvolgimento di BRCA1 nella cancerogenesi.
La localizzazione della proteina è influenzata dalla posizione della mutazione, infatti i dati statisticamente più rilevanti si riferiscono alle varianti del dominio BRCT evidenziando il ruolo del dominio stesso.
La riparazione invece risente molto del tipo di mutazione. L’espressione di varianti patogenetiche di BRCA1 provoca un aumento della ricombinazione sia intra- che intercromosomica solamente iniziale, infatti la frequenza si uguaglia alle varianti neutre. L’espressione della proteina nelle sue forme neutre, in presenza dell’agente alchilante permette una maggiore riparazione del danno favorendo allo stesso modo sia un aumento della ricombinazione intra- ed intercromosomica.
Alla luce di questi risultati possiamo concludere che il lievito sia un valido organismo modello nonostante non presenti l’omologo di BRCA1, in quanto ha evidenziato le differenze tra le varianti nei pathway analizzati.
In futuro, sarebbe interessante valutare l’effetto sulla riparazione del DNA dopo danno indotto anche su ceppi deleti di geni della riparazione come RAD50, RAD51, MRE11 e MSH6.
Altre analisi verranno comunque effettuate su altre varianti per poter validare il saggio funzionale al fine di discriminare le varianti neutre da quelle patogenetiche.
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Bibliografia
Abbott DW, Thompson ME, Robinson-Benion C, Tomlinson G, Jensen RA, Holt JT. (1999). BRCA1 expression restores radiation resistance in BRCA1-defective cancer cells through enhancement of transcription-coupled DNA repair. J Biol.Chem. 274(26):18808–18812.
Anderson SF, Schlegel BP, Nakajima T, Wolpin ES and Parvin JD. (1998). BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A.Nat. Genet. 19,254-256.
Andrews CA and Clarke DJ. (2005). MRX (Mre11/Rad50/Xrs2) mutants reveal dual intra-S-phase checkpoint systems in budding yeast. Cell Cycle 4(8):1073-7.
Antoniou AC, Easton DF. (2006). Models of genetic susceptibility to breast cancer. Oncogene 25(43):5898-905.
Au WW, Henderson BR. (2005). The BRCA1 RING and BRCT domains cooperate in targeting BRCA1 to ionizing radiation-induced nuclear foci. J Biol.Chem. 280(8):6993–7001.
Baer R, Ludwig T. (2002). The BRCA1/BARD1 heterodimer, a tumor suppressor complex with ubiquitin E3 ligase activity. Current Opinion In Genetics and Development 12(1):86–91.
Bakkenist CJ and Kastan MB. (2015). Chromatin perturbations during the DNA damage response in higher eukaryotes. DNA Repair. pii: S1568-7864(15)00177-9. Baldeyron C, Jacquemin E, Smith J, Jacquemont C, De OI, Gad S, Feunteun J, Stoppa - Lyonnet D, Papadopoulo D. (2002). A single mutated BRCA1 allele leads to impaired fidelity of double strand break end-joining. Oncogene 21(9):1401–1410. Bennett CB, Westmoreland TJ, Verrier CS, Blanchette CAB, Sabin TL, Phatnani HP, Mishina YV, Huper G, Selim AL, Madison ER, Bailey DD, Falae AI, et al. (2008). Yeast Screens Identify the RNA Polymerase II CTD and SPT5 as Relevant Targets of BRCA1 Interaction. PLoS ONE 3(1):e1448.
85
Beranek DT. (1990). Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents Mutat. Res. 23111–30.
Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS, Wang W, Kashanchi F and Shiekhattar R. (2000). BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin remodeling to breast cancer. Cell 102,257-265.
Botuyan MV, Nomine Y, Yu X, Juranic N, Macura S, Chen J, Mer G. (2004). Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains. Structure. (Camb.) 12(7):1137–1146.
Caligo MA, Bonatti F, Guidugli L, Aretini P, Galli A. (2009). A yeast recombination assay to characterize human BRCA1 missense variants of unknown pathological significance. Hum Mutat 30(1):123–133.
Cantor SB, Bell DW, Ganesan S, Kass EM, Drapkin R, Grossman S, Wahrer DC, Sgroi DC, Lane WS, Haber DA and Livingston DM. (2001). BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function. Cell 105, 149-160.
Carr AM. (2000). Cell cycle.Piecing together the p53 puzzle. Science 287,1765-1766. Carvalho MA, Couch FJ, Monteiro AN. (2007a). Functional assays for BRCA1 and
BRCA2.Int.J.Biochem.Cell Biol. 39(2):298–310.
Carvalho MA, Marsillac SM, Karchin R, Manoukian S, Grist S, Swaby RF, Urmenyi TP, Rondinelli E, Silva R, Gayol L, Baumbach L, Sutphen R, et al. (2007b). Determination of Cancer Risk Associated with Germ Line BRCA1 Missense Variants by Functional Analysis. Cancer Research 67(4):1494–1501.
Carvalho MA, Billack B, Chan E, Worley T, Cayanan C, Monteiro AN. (2002). Mutations in the BRCT Domain Confer Temperature Sensitivity to BRCA1 in Transcription Activation.Cancer Biol.Ther 1(5):502–508.
Chang S, Biswas K, Martin BK, Stauffer S, Sharan SK. (2009). Expression of human BRCA1 variants in mouse ES cells allows functional analysis of BRCA1 mutations. J Clin Invest 119(10):3160–3171.
86
Chen Y, Farmer AA, Chen CF, Jones DC, Chen PL, Lee WH. (1996). BRCA1 is a 220- kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle- dependent manner [published erratum appears in Cancer Res 1996 Sep 1;56(17):4074] Cancer Res. 56(14):3168–3172.
Clapperton JA, Manke IA, Lowery DM, Ho T, Haire LF, Yaffe MB, Smerdon SJ. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct.Mol.Biol. 11(6):512–518.
Coene ED, Hollinshead MS, Waeytens AA, Schelfhout VR, Eechaute WP, Shaw MK, Van Oostveldt PM, Vaux DJ. (2005). Phosphorylated BRCA1 is predominantly located in the nucleus and mitochondria. Mol.Biol Cell 16(2):997–1010.
Collavoli A, Comelli L, Rainaldi G and Galli A. (2008). A yeast-based genetic screening to identify human proteins that increase homologous recombination. FEMS Yeast Research Volume 8, Issue 3, pages 351–361.
Connor F, Bertwistle D, Mee PJ, Ross GM, Swift S, Grigorieva E, Tybulewicz VL and Ashworth A. (1997a). Tumorigenesis and a DNA repair defect in mice with a truncating BRCA2 mutation. Nat. Genet. 17,423-430.
Cortez D, Wang Y, Qin J, Elledge SJ. (1999). Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science 286(5442):1162–1166.
Coyne RS, McDonald HB, Edgemon K, Brody LC. (2004). Functional Characterization of BRCA1 Sequence Variants Using a Yeast Small Colony Phenotype Assay. Cancer Biol.Ther. 3(5):453–457.
Dapic V, Monteiro AN. (2006). Functional implications of BRCA1 for early detection, prevention, and treatment of breast cancer.Crit Rev. Eukaryot. Gene Expr. 16(3):233–252.
Deng CX. (2001). Tumorigenesis as a consequence of genetic instability in Brca1 mutant mice. Mutat Res. 477(1-2):183-9.
87
Douzery EJP, Snell EA, Bapteste E, Delsuc F, Philippe H. (2004). The timing of eukaryotic evolution: Does a relaxed molecular clock reconcile proteins and fossils?. Proc. Natl. Acad. Sci. U.S.A. 101, 15386-15391.
Drost R, Bouwman P, Rottenberg S, Boon U, Schut E, Klarenbeek S, Klijn C, van der Heijden I, van der Gulden H, Wientjens E, Pieterse M, Catteau A, et al. (2011). BRCA1 RING function is essential for tumor suppression but dispensable for therapy resistance.Cancer Cell 20(6):797–809.
Erkko H, Xia B, Nikkila J, Schleutker J, Syrjakoski K, Mannermaa A, Kallioniemi A, Pylkas K, Karppinen SM, Rapakko K, Miron A, Sheng Q, Li G, Mattila H, Bell DW, Haber DA, Grip M, Reiman M, Jukkola-Vuorinen A, Mustonen A, Kere J, Aaltonen LA, Kosma VM, Kataja V, Soini Y, Drapkin RI, Livingston DM, Winqvist R. (2007). A recurrent mutation in PALB2 in Finnish cancer families. Nature 446 (7133):316- 9.
Fanale D, Amodeo V, Corsini LR, Rizzo S, Bazan V, Russo A. (2012). Breast cancer genome-wide association studies: there is strength in numbers. Oncogene 31(17):2121 8.
Feng Z, Kachnic L, Zhang J, Powell SN, Xia F. (2004). DNA damage induces p53- dependent BRCA1 nuclear export. J Biol.Chem 279(27):28574–28584.
Galli A and Schiestl RH (1995). On the mechanism of UV and γ-ray-induced intrachromosomal recombination in yeast cells synchronized in different stages of the cell cycle. Molecular and General Genetics MGG. 248, Issue 3, pp 301-310. Galli A and Schiestl RH (1999). Cell division transforms mutagenic lesions into
deletion-recombinagenic lesions in yeast cells. Mutation Research 429 13–26. German J. (1993). Bloom syndrome: a Mendelian prototype of somatic mutational
disease. Medicine 72, 393-406.
Gietz RD, Schiestl RH. (2007). High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method. Nat Protoc 2(1):31-4.
88
Golub EI, Kovalenko OV, Gupta RC, Ward DC, Radding CM. (1997). Interaction of human recombination proteins Rad51 and Rad54. Nucleic Acids Res 25(20):4106- 10.
Gowen LC, Avrutskaya AV, Latour AM, Koller BH and Leadon SA. (1998). BRCA1 required for transcription-coupled repair of oxidative DNA damage. Science 281,1009-1012.
Harkin DP, Bean JM, Miklos D, Song YH, Truong VB, Englert C, Christians FC, Ellisen LW, Maheswaran S, Oliner JD and Haber DA. (1999). Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1. Cell 97, 575-586.
Hartwell LH. (2004) Yeast and cancer.Biosci. Rep. 24, 523-544.
Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H and Ohta T. (2001). The ring heterodimer brca1-bard1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation.J. Biol. Chem. 276,14537-14540.
Hong SP. et al., (2003). Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases. Proc. Natl. Acad. Sci. U.S.A. 100, 8839-8843. Hughes AL. et al., (2005). SREBP pathway responds to sterols and functions as an
oxygen sensor in fission yeast. Cell 120, 831-842.
Hughes AL et al., (2007). Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes. Cell. Metab. 5, 143-149.
Humphrey JS, Salim A, Erdos MR, Collins FS, Brody LC, Klausner RD. (1997). Human BRCA1 inhibits growth in yeast: potential use in diagnostic testing. Proc Natl Acad Sci U S A 94(11):5820–5825.
Irwin B et al., (2005). Retroviruses and yeast retrotrasposons use overlapping sets of host genes. Genome Res. 15, 641-654.
Jhuraney Ankita et al., (2015). “BRCA1 Circos: A Visualisation Resource for Functional Analysis of Missense Variants.” Journal of Medical Genetics 52.4 (2015): 224–230. PMC.Web.
89
Jin Y, Xu XL, Yang MC, Wei F, Ayi TC, Bowcock AM, Baer R. (1997). Cell cycle- dependent colocalization of BARD1 and BRCA1 proteins in discrete nuclear domains. Proc Natl Acad Sci U S A 94(22):12075–12080.
Kachroo AH, Laurent JM, Yellman CM, Meyer AG, Wilke CO, Marcotte EM. (2015). Systematic humanization of yeast genes reveals conserved functions and genetic modularity. Science 348(6237) 921-925.
Kaeberlein M, Burtner CR, Kennedy BK. (2007). Recent Developments in Yeast Aging. Plos Collection 10.1371/journal.pgen.0030084.
Kais Z, Chiba N, Ishioka C, Parvin JD. (2011). Functional differences among BRCA1 missense mutations in the control of centrosome duplication. Oncogene 31(6):799–804.
Kitao H, Yuan ZM. (2002). Regulation of ionizing radiation-induced Rad52 nuclear foci formation by c-Abl-mediated phosphorylation. J Biol Chem. 277(50):48944-8. Kleiman FE and Manley JL. (1999). Functional interaction of BRCA1-associated
BARD1 with polyadenylation factor CstF-50. Science 285,1576-1579.
Kleiman FE and Manley JL. (2001). The BARD1-CstF-50 interaction links mRNA 3′ end formation to DNA damage and tumor suppression. Cell 104,743-753.
Kote-Jarai Z, Matthews L, Osorio A, Shanley S, Giddings I, Moreews F, Locke I, Evans DG, Eccles D, Williams RD, Girolami M, Campbell C, et al,. (2006). Accurate prediction of BRCA1 and BRCA2 heterozygous genotype using expression profiling after induced DNA damage. Clin Cancer Res 12(13):3896–3901.
Lalloo F, Evans DG. (2012). Familial breast cancer. Clin Genet. 82(2):105-14.
Lee MS, Green R, Marsillac SM, Coquelle N, Williams RS, Yeung T, Foo D, Hau DD, Hui B, Monteiro AN, Glover JN. (2010). Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. Cancer Res. 70(12):4880–4890.
Le Page F, Randrianarison V, Marot D, Cabannes J, Perricaudet M, Feunteun J and Sarasin A. (2000). BRCA1 and BRCA2 are necessary for the transcription-coupled
90
repair of the oxidative 8-oxoguanine lesion in human cells. Cancer Res. 60,5548- 5552.
Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD and Lee WH. (1999). Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage.J. Biol. Chem. 274,11334-11338.
Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY and Lee WH. (2000). Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature 406,210-215.
Lindahl T and Wood RD. (1999). Quality control by DNA repair Science2861897– 1905.
Lundin C, North M, Erixon K, Walters K, Jenssen D, Goldman ASH, Helleday T. (2005). Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks. Nucl Acids Res 33:3799-811.
Madeo F et al., (2004). Apoptosis in yeast. Curr.Opin.Microbiol. 7, 655-660.
Manger WH and Winderickx J. (2005). Yeast as a model for medical and medicinal research. Trends Pharmacol Sci. 26(5):265-73.
Maresca L, Spugnesi L, Lodovichi S, Cozzani C, Naccarato AG, Tancredi M, Collavoli A, Falaschi E, Rossetti E, Aretini P, Cervelli T, Galli A, Caligo MA. (2015). MSH2 role in BRCA1-driven tumorigenesis: a preliminary study in yeast and in human tumors from BRCA1-VUS carriers, European Journal of Medical Genetics doi: 10.1016/j.ejmg.2015.09.005.
Millot GA, Berger A, Lejour V, Boule JB, Bobo C, Cullin C, Lopes J, Stoppa-Lyonnet D, Nicolas A. (2011). Assessment of human Nter and Cter BRCA1 mutations using growth and localization assays in yeast. Hum Mutat 32(12):1470–1480.
Millot et al., (2012). “A Guide for Functional Analysis of BRCA1 Variants of Uncertain Significance (VUS).” Human mutation 33.11: 1526–1537.
91
Monteiro AN, August A, Hanafusa H. (1996). Evidence for a transcriptional activation function of BRCA1 C-terminal region. Proc. Natl. Acad. Sci. U.S.A. 93(24):13595–13599.
Monteiro AN, Humphrey JS. (1998). Yeast-based assays for detection and characterization of mutations in BRCA1. Breast Disease 10:61–70.
Monteiro AN, Birge RB. (2000). A nuclear function for the tumor suppressor BRCA1. Histology and Histopathology. 15(1):299–307.
Morris JR, Pangon L, Boutell C, Katagiri T, Keep NH, Solomon E. (2006). Genetic analysis of BRCA1 ubiquitin ligase activity and its relationship to breast cancer susceptibility. Human Molecular Genetics 15(4):599–606.
Myung K and Kolodner RD. (2003) Induction of genome instability by DNA damage in Saccharomyces cerevisiae DNA Repair 2243–258.
Narod SA, Foulkes WD. (2004). BRCA1 and BRCA2: 1994 and beyond. Nat.Rev.Cancer. 4(9):665–676.
Nurse PM. (2002) Nobel Lecture. Cyclin dependent kinases and cell cycle control. Biosci. Rep. 22, 487-499.
O’Brien KP, Remm M, Sonnhammer ELL. (2005). Nucleic Acids Res. 33, D476-D480.
Ocampo A and Barrientos A. (2008). From the bakery to the brain business: developing inducible yeast models of human neurodegenerative disorders. Biotechniques 45(4):Pvii-xiv.
Ouellette M.M. et al., (2000). The establishment of telomerase-immortalized cell lines representing human chromosome instability syndromes. Hum. Mol. Genet. 9, 403-411.
Outeiro TF and Muchowski PJ. (2004). Molecular genetics approaches in yeast to study amyloid disease. J. Mol. Neurosci. 23, 49-60.
92
Pao GM, Janknecht R, Ruffner H, Hunter T and Verma IM. (2000). CBP/p300 interact with and function as transcriptional coactivators of BRCA1.Proc. Natl. Acad. Sci. USA 97, 1020-1025.
Pardo B, Gomez-Gonzalez B, Aguilera A. (2009). DNA repair in mammalian cells: DNA doublestrand break repair: how to fix a broken relationship. Cell Mol Life Sci. 66(6):1039-56.
Parkin DM, Bray F, Ferlay J, Pisani P. (2005). Global cancer statistics, 2002. CA Cancer J Clin. 55(2):74-108.
Patel KJ, Yu VPCC, Lee H, Corcoran A, Thistlethwaite FC, Evans MJ, Colledge WH, Friedman LS, Ponder BA and Venkitaraman AR. (1998). Involvement of BRCA2 in DNA repair. Mol. Cell1, 347-357.
Perocchi F et al., (2008). Systematic screens for human disease genes, frome yeast to human and back. Mol. Biosyst. 4, 18-29.
Petermann E, Orta ML, Issaeva N, Schultz N, Helleday T. (2010). Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair. Mol Cell. 37(4):492-502.
Petranovic D, Nielsen J. (2008). Can yeast systems biology contribute to the understandin of human disease?.Trends Biotechnol. 26:584-590.
Phelan CM, Dapic V, Tice B, Favis R, Kwan E, Barany F, Manoukian S, Radice P, van der Luijt RB, van Nesselrooij BP, Chenevix-Trench G, kConFab, et al., (2005) Classification of BRCA1 missense variants of unknown clinical significance. J Med Genet 42(2):138–146.
Pierce AJ, Stark JM, Araujo FD, Moynahan ME, Berwick M, Jasin M. (2001). Double- strand breaks and tumorigenesis. Trends Cell Biol. 11(11):S52-9.
Ransburgh DJ, Chiba N, Ishioka C, Toland AE, Parvin JD. (2010). Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination. Cancer Res. 70(3):988–995.
93
Richardson C, Jasin M. (2000). Coupled homologous and nonhomologous repair of a double-strand break preserves genomic integrity in mammalian cells. Mol Cell Biol. 20(23):9068-75.
Rodriguez JA, Henderson BR. (2000). Identification of a functional nuclear export sequence in BRCA1. J Biol.Chem 275(49):38589–38596.
Rodriguez M, Yu X, Chen J, Songyang Z. (2003). Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains. J Biol.Chem. 278(52):52914–52918. Rodriguez JA, Au WW, Henderson BR. (2004a). Cytoplasmic mislocalization of
BRCA1 caused by cancer-associated mutations in the BRCT domain. Exp. Cell Res 293(1):14–21.
Rodriguez JA, Schuchner S, Au WW, Fabbro M, Henderson BR. (2004b). Nuclear- cytoplasmic shuttling of BARD1 contributes to its proapoptotic activity and is regulated by dimerization with BRCA1. Oncogene 23(10):1809–1820.
Ruffner H, Joazeiro CA, Hemmati D, Hunter T and Verma IM. (2001). Cancer- predisposing mutations within the RING domain of BRCA1: loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Proc. Natl. Acad. Sci. USA 98,5134-5139.
Sarkar M, Magliery TJ. (2008). Re-engineering a split-GFP reassembly screen to examine RING-domain interactions between BARD1 and BRCA1 mutants observed in cancer patients.Mol Biosyst 4(6):599–605.
Savage KI and Harkin DP. (2015). BRCA1, a 'complex' protein involved in the maintenance of genomic stability. FEBS J. 282(4):630-46.
Scully R, Ganesan S, Brown M, De Caprio JA, Cannistra SA, Feunteun J, Schnitt S, Livingston DM. (1996). Location of BRCA1 in human breast and ovarian cancer cells. Science 272(5258):123–126.
Scully R, Chen J, Ochs RL, Keegan K, Hoekstra M, Feunteun J, Livingston DM. (1997a). Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage. Cell 90(3):425–435.
94
Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM. (1997b). Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell. 88(2):265–275.
Scully R, Ganesan S, Vlasakova K, Chen J, Socolovsky M, Livingston DM. (1999). Genetic analysis of BRCA1 function in a defined tumor cell line. Mol.Cell 4(6):1093–1099.
Scully R, Livingston D. (2000). In search of the tumour-suppressor functions of BRCA1 and BRCA2. Nature. 408:429–432.
Shakya R, Reid LJ, Reczek CR, Cole F, Egli D, Lin CS, deRooij DG, Hirsch S, Ravi K, Hicks JB, Szabolcs M, Jasin M, Baer R, Ludwig T. (2011). BRCA1 tumor suppression depends on BRCT phosphoprotein binding, but not its E3 ligase activity. Science 334(6055):525-8.
Sharan SK, Morimatsu M, Albrecht U, Lim D, Regel E, Dinh C, Sands A, Eichele G, Hasty P and Bradley A. (1997). Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking BRCA2. Nature 386, 804-810.
Shen SX, Weaver Z, Xu X, Li C, Weinstein M, Chen L, Guan XY, Ried T, Deng CX. (1998). A targeted disruption of the murine Brca1 gene causes gamma- irradiation hypersensitivity and genetic instability. Oncogene 17(24):3115–3124. Shiozaki EN, Gu L, Yan N, Shi Y. (2004). Structure of the BRCT repeats of BRCA1
bound to a BACH1 phosphopeptide: implications for
signaling. Mol.Cell 14(3):405–412.
Siciliano PD, Parker AL, Lawrence LM. (1997). Effect of dietary vitamin E supplementation on the integrity of skeletal muscle in exercised horses. J Anim Sci. 75(6):1553-60.
Somasundaram K, Zhang H, Zeng YX, Houvras Y, Peng Y, Wu GS, Licht JD, Weber BL and El-Deiry WS. (1997). Arrest of the cell cycle by the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAF1/CiP1. Nature 389,187-190.
95
Starita LM, Machida Y, Sankaran S, Elias JE, Griffin K, Schlegel BP, Gygi SP, Parvin JD. (2004). BRCA1-dependent ubiquitination of gamma-tubulin regulates centrosome number. Mol.Cell Biol 24(19):8457–8466.
Steinmetz, E.J..et al. (2004) Genome-wide distribution of yeast RNA polymerase II and its control by Sen1 helicase. Mol. Cell. 24, 735-746.
Tomlinson GE, Chen TT, Stastny VA, Virmani AK, Spillman MA, Tonk V, Blum JL, Schneider NR, Wistuba II, Shay JW, Minna JD, Gazdar AF. (1998). Characterization of a breast cancer cell line derived from a germ-line BRCA1 mutation carrier. Cancer Res. 58(15):3237–3242.
Vallon-Christersson J, Cayanan C, Haraldsson K, Loman N, Bergthorsson JT, Brondum-Nielsen K, Gerdes AM, Moller P, Kristoffersson U, Olsson H, Borg A, Monteiro AN. (2001). Functional analysis of BRCA1 C-terminal missense mutations identified in breast and ovarian cancer families.Human Molecular Genetics 10(4):353–360.
Venkitaraman AR. (2001). Functions of BRCA1 and BRCA2 in the biological response to DNA damage. Journal of Cell Science.
Waddell N, Ten HA, Marsh A, Johnson J, Walker LC, Investigators K, Gongora M, Brown M, Grover P, Girolami M, Grimmond S, Chenevix-Trench G, et al., (2008). BRCA1 and BRCA2 missense variants of high and low clinical significance influence lymphoblastoid cell line post-irradiation gene expression. PLoS Genet. 4(5) e1000080.
Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ and Qin J. (2000). BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. 14,927-939.
Wang B, Matsuoka S, Ballif BA, Zhang D, Smogorzewska A, Gygi SP, Elledge SJ. (2007). Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science 316(5828):1194-8.
96
Wang H, Yang ES, Jiang J, Nowsheen S, Xia F. (2010). DNA damage-induced cytotoxicity is dissociated from BRCA1's DNA repair function but is dependent on its cytosolic accumulation. Cancer Res 70(15):6258–6267.
Wang H, Shao Z, Shi LZ, Hwang PY, Truong LN, Berns MW, Chen DJ, Wu X. (2012). CtIP protein dimerization is critical for its recruitment to chromosomal DNA double-stranded breaks. J Biol Chem. 287(25):21471-80.
Williams RS, Green R, Glover JN. (2001). Crystal structure of the BRCT repeat region from the breast cancer- associated protein BRCA1. Nat Struct. Biol 8(10):838– 842.
Williams RS, Chasman DI, Hau DD, Hui B, Lau AY, Glover JN. (2003). Detection of protein folding defects caused by BRCA1-BRCT truncation and missense mutations. J Biol.Chem. 278(52):53007–53016.
Williams RS, Glover JN. (2003). Structural consequences of a cancer-causing BRCA1- BRCT missense mutation. J Biol.Chem 278(4):2630–2635.
Williams RS, Lee MS, Hau DD, Glover JN. (2004). Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1.Nat Struct.Mol.Biol. 11(6):519–525. Wong AKC, Pero R, Ormonde PA, Tavtigian SV and Bartel PL. (1997). RAD51 interacts
with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene BRCA2. J. Biol. Chem. 272, 31941-31944.
Workman CT et al., (2006). A systems approach to mapping DNA damage response pathways. Science 312, 1054-1059.
Wu-Baer F, Lagrazon K, Yuan W, Baer R. (2003). The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving