Chromatin acetylation, β-amyloid precursor protein and its binding partner FE65 in DNA double strand break repair
Among post-translational modifications of chromatin proteins taking place in DNA double strand break (DSB) repair, acetylation plays a prominent role. This review lists several facts and hypotheses concerning this process. Lack of acetyltransferase TIP60 (HIV-Tat interacting protein of 60 kDa) activity results in cells with defective DSB repair. The enzyme is present in the nucleus in a multimeric protein complex. TIP60 dependent activation of ATM (ataxia telangiectasia mutated kinase) is an early event in the response to DNA breakage. Other important acetylations are those of histones H4 and γH2AX. Correct reconstruction of the damaged site is critical for survival and prevention of genetic and epigenetic changes in the cell that may affect the function of its daughter cells. Recently, two proteins with previously unsuspected functions in DSB repair have been identified as active in this process: Alzheimer β-amyloid precursor protein (APP) and its binding partner FE65, β-amyloid precursor binding protein. Their participation in DSB repair in both neuronal and non-neuronal cells is related to acetylation carried out by the acetyltransferase complex. The same function is ascribed to heterochromatin protein 1 (HP1). So far, the relations (if any) between TIP60 activation by HP1 and by the FE65 complex remain unidentified.
- Altaf M, Saksouk N, Côté J (2007) Histone modifications in response to DNA damage. Mutat Res 618: 81-90.
- Ayoub N, Jeyasekharan AD, Bernal JA, Venkitaraman AR (2008) HP1-beta mobilization promotes chromatin changes that initiate the DNA damage response. Nature 453: 682-686.
- Ayoub N, Jeyasekharan AD, Venkitaraman AR (2009) Mobilization and recruitment of HP1, a bimodal response to DNA breakage. Cell Cycle 8: 2945-2950.
- Ball AR Jr, Yokomori K (2009) Revisiting the role of heterochromatin protein 1 in DNA repair. J Cell Biol 185: 573-575.
- Borg JP, Ooi J, Levy E, Margolis B (1996) The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. Mol Cell Biol 16: 6229-6241.
- Cai Y, Jin J, Swanson SK, Cole MD, Choi SH, Florens L, Washburn MP, Conaway JW, Conaway RC (2010) Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex. J Biol Chem 285: 4268-4272.
- Cao X, Südhof TC (2001) A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293: 115-120.
- Cao X, Südhof TC (2004) Dissection of amyloid-beta precursor protein-dependent transcriptional transactivation. J Biol Chem 279: 24601-24611.
- Cervoni N, Szyf M (2001) Demethylase activity is directed by histone acetylation. J Biol Chem 276: 40778-40787.
- Cervoni N, Detich N, Seo SB, Chakravarti D, Szyf M (2002) The oncoprotein Set/TAF-1beta, an inhibitor of histone acetyltransferase, inhibits active demethylation of DNA, integrating DNA methylation and transcriptional silencing. J Biol Chem 277: 25026-25031.
- Chen L, Lee L, Kudlow BA, Dos Santos HG, Sletvold O, Shafeghati Y, Botha EG, Garg A, Hanson NB, Martin GM, Mian IS, Kennedy BK, Oshima J (2003) LMNA mutations in atypical Werner's syndrome. Lancet 362: 440-445.
- Chailleux C, Tyteca S, Papin C, Boudsocq F, Puget N, Courilleau C, Grigoriev M, Canitrot Y, Trouche D (2010) Physical interaction between the histone acetyl transferase Tip60 and the DNA double-strand breaks sensor MRN complex. Biochem J 426: 365-371.
- Constantinescu D, Csoka AB, Navara CS, Schatten GP (2010) Defective DSB repair correlates with abnormal nuclear morphology and is improved with FTI treatment in Hutchinson-Gilford progeria syndrome fibroblasts. Exp Cell Res 316: 2747-2759.
- Costes SV, Chiolo I, Pluth JM, Barcellos-Hoff MH, Jakob B (2010) Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization. Mutat Res 704: 78-87.
- de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370: 737-749.
- Dinant C, Luijsterburg MS (2009) The emerging role of HP1 in the DNA damage response. Mol Cell Biol 29: 6335-6340.
- Doyon Y, Côté J (2004) The highly conserved and multifunctional NuA4 HAT complex. Curr Opin Genet Dev 14: 147-154.
- Eot-Houllier G, Fulcrand G, Magnaghi-Jaulin L, Jaulin C (2009) Histone deacetylase inhibitors and genomic instability. Cancer Lett 274: 169-176.
- Ermekova KS, Zambrano N, Linn H, Minopoli G, Gertler F, Russo T, Sudol M (1997) The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled. J Biol Chem 272: 32869-32877.
- Fiore F, Zambrano N, Minopoli G, Donini V, Duilio A, Russo T (1995) The regions of the Fe65 protein homologous to the phosphotyrosine interaction/phosphotyrosine binding domain of Shc bind the intracellular domain of the Alzheimer's amyloid precursor protein. J Biol Chem 270: 30853-30856.
- Geng L, Cuneo KC, Fu A, Tu T, Atadja PW, Hallahan DE (2006) Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Cancer Res 66: 11298-11304.
- Giliberto L, Zhou D, Weldon R, Tamagno E, De Luca P, Tabaton M, D'Adamio L (2008) Evidence that the amyloid beta precursor protein-intracellular domain lowers the stress threshold of neurons and has a "regulated" transcriptional role. Mol Neurodegener 3: 12.
- Goodarzi AA, Noon AT, Deckbar D, Ziv Y, Shiloh Y, Löbrich M, Jeggo PA (2008) ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol Cell 31: 167-177.
- Goodarzi, AA, Noon AT, Jeggo PA (2009) The impact of heterochromatin on DSB repair. Biochem Soc Trans 37: 569-576.
- Gupta A, Sharma GG, Young CS, Agarwal M, Smith ER, Paull TT, Lucchesi JC, Khanna KK, Ludwig T, Pandita TK (2005) Involvement of human MOF in ATM function. Mol Cell Biol 25: 5292-5305.
- Hajji N, Wallenborg K, Vlachos P, Füllgrabe J, Hermanson O, Joseph B (2010) Opposing effects of hMOF and SIRT1 on H4K16 acetylation and the sensitivity to the topoisomerase II inhibitor etoposide. Oncogene 29: 2192-2204.
- Hass MR, Yankner BA (2005) A γ-secretase-independent mechanism of signal transduction by the amyloid precursor protein. J Biol Chem 280: 36895-36904.
- Huertas P (2010) DNA resection in eukaryotes, deciding how to fix the break. Nat Struct Mol Biol 17: 11-16.
- Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M, Scully R, Qin J, Nakatani Y (2000) Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell 102: 463-473.
- Kataoka Y, Murley JS, Baker KL, Grdina DJ (2007) Relationship between phosphorylated histone H2AX formation and cell survival in human microvascular endothelial cells (HMEC) as a function of ionizing radiation exposure in the presence or absence of thiol-containing drugs. Radiat Res 168: 106-114.
- Khochbin S, Verdel A, Lemercier C, Seigneurin-Berny D (2001) Functional significance of histone deacetylase diversity. Curr Opin Genet Dev 11: 162-166.
- Kimberly WT, Zheng JB, Guénette SY, Selkoe DJ (2001) The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. J Biol Chem 276: 40288-40292.
- Kinoshita A, Whelan CM, Smith CJ, Berezovska O, Hyman BT (2002a) Direct visualization of the gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein, association with Fe65 and translocation to the nucleus. J Neurochem 82: 839-847.
- Kinoshita A, Whelan CM, Berezovska O, Hyman BT (2002b) The gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 Cells. J Biol Chem 277: 28530-28536.
- Kwon SH, Workman JL (2008) The heterochromatin protein 1 (HP1) family, put away a bias toward HP1. Mol Cells 26: 217-227.
- Lee KK, Workman JL (2007) Histone acetyltransferase complexes: one size doesn't fit all. Nat Rev Mol Cell Biol 8: 284-295.
- Lee MS, Kao SC, Lemere CA, Xia W, Tseng HC, Zhou Y, Neve R, Ahlijanian MK, Tsai LH (2003) APP processing is regulated by cytoplasmic phosphorylation. J Cell Biol 163: 83-95.
- Li M, Makkinje A, Damuni Z (1996) The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A. J Biol Chem 271: 11059-11062.
- Li X, Wu L, Corsa CA, Kunkel S, Dou Y (2009) Two mammalian MOF complexes regulate transcription activation by distinct mechanisms. Mol Cell 36: 290-301.
- Liao YF, Wang BJ, Cheng HT, Kuo LH, Wolfe MS (2004) Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J Biol Chem 279: 49523-49532.
- Lieber MR (2010) The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 79: 181-211.
- Lisby M, Rothstein R (2009) Choreography of recombination proteins during the DNA damage response. DNA Repair 8: 1068-1076.
- Lopez-Lopez C, Dietrich MO, Metzger F, Loetscher H, Torres-Aleman I (2007) Disturbed cross talk between insulin-like growth factor I and AMP-activated protein kinase as a possible cause of vascular dysfunction in the amyloid precursor protein/presenilin 2 mouse model of Alzheimer's disease. J Neurosci 27: 824-831.
- Luijsterburg MS, Dinant C, Lans H, Stap J, Wiernasz E, Lagerwerf S, Warmerdam DO, Lindh M, Brink MC, Dobrucki JW, Aten JA, Fousteri MI, Jansen G, Dantuma NP, Vermeulen W, Mullenders LH, Houtsmuller AB, Verschure PJ, van Driel R (2009) Heterochromatin protein 1 is recruited to various types of DNA damage. J Cell Biol 185: 577-586.
- Mahaney BL, Meek K, Lees-Miller SP (2009) Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining. Biochem J 417: 639-650.
- Mimitou EP, Symington LS (2009) DNA end resection: many nucleases make light work. DNA Repair 8: 983-995.
- Minopoli G, Stante M, Napolitano F, Telese F, Aloia L, De Felice M, Di Lauro R, Pacelli R, Brunetti A, Zambrano N, Russo T (2007) Essential roles for Fe65, Alzheimer amyloid precursor-binding protein, in the cellular response to DNA damage. J Biol Chem 282: 831-835.
- Moon SH, Nguyen TA, Darlington Y, Lu X, Donehower LA (2010) Dephosphorylation of gammaH2AX by WIP1, an important homeostatic regulatory event in DNA repair and cell cycle control. Cell Cycle 9: 2092-2096.
- Müller T, Meyer HE, Egensperger R, Marcus K (2008) The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-relevance for Alzheimer's disease. Prog Neurobiol 85: 393-406.
- Murr R, Loizou JI, Yang YG, Cuenin C, Li H, Wang ZQ, Herceg Z (2006) Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks. Nat Cell Biol 8: 91-99.
- Murr R, Vaissière T, Sawan C, Shukla V, Herceg Z (2007) Orchestration of chromatin-based processes: mind the TRRAP. Oncogene 26: 5358-5372.
- Muto S, Senda M, Akai Y, Sato L, Suzuki T, Nagai R, Senda T, Horikoshi M (2007) Relationship between the structure of SET/TAF-Ibeta/INHAT and its histone chaperone activity. Proc Natl Acad Sci USA 104: 4285-4290.
- Nakamura AJ, Rao VA, Pompier Y, Bonnier WM (2010) The complexity of phosphorylated H2AX foci formation and DNA repair assembly at DNA double-strand breaks. Cell Cycle 9: 389-397.
- Nakaya T, Suzuki T (2006) Role of APP phosphorylation in FE65-dependent gene transactivation mediated by AICD. Genes Cells 11: 633-645.
- Narang H, Bhat N, Gupta S, Santra S, Choudhary RK, Kailash S, Krishna M (2009) Differential activation of mitogen-activated protein kinases following high and low LET radiation in murine macrophage cell line. Mol Cell Biochem 324: 85-91.
- Nikolaev A, McLaughlin T, O'Leary DD, Tessier-Lavigne M (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457: 981-989.
- Noon AT, Shibata A, Rief N, Löbrich M, Stewart GS, Jeggo PA, Goodarzi AA (2010) 53BP1-dependent robust localized KAP-1 phosphorylation is essential for heterochromatic DNA double-strand break repair. Nat Cell Biol 12: 177-184.
- Pandita TK, Richardson C (2009) Chromatin remodeling finds its place in the DNA double-strand break response. Nucleic Acids Res 37: 1363-1377.
- Pardo B, Gómez-González B, Aguilera A (2009) DNA repair in mammalian cells, DNA double-strand break repair, how to fix a broken relationship. Cell Mol Life Sci 66: 1039-1056.
- Perkinton MS, Standen CL, Lau KF, Kesavapany S, Byers HL, Ward M, McLoughlin DM, Miller CC (2004) The c-Abl tyrosine kinase phosphorylates the Fe65 adaptor protein to stimulate Fe65/amyloid precursor protein nuclear signaling. J Biol Chem 279: 22084-22091.
- Reinhard C, Hébert SS, De Strooper B (2005) The amyloid-beta precursor protein, integrating structure with biological function. EMBO J 24: 3996-4006.
- Robert F, Hardy S, Nagy Z, Baldeyron C, Murr R, Déry U, Masson JY, Papadopoulo D, Herceg Z, Tora L (2006) The transcriptional histone acetyltransferase cofactor TRRAP associates with the MRN repair complex and plays a role in DNA double-strand break repair. Mol Cell Biol 26: 402-412.
- Russo T, Faraonio R, Minopoli G, De Candia P, De Renzis S, Zambrano N (1998) Fe65 and the protein network centered around the cytosolic domain of the Alzheimer's beta-amyloid precursor protein. FEBS Lett 434: 1-7.
- Sapountzi V, Logan IR, Robson CN (2006) Cellular functions of TIP60. Int J Biochem Cell Biol 38: 1496-1509.
- Seo SB, McNamara P, Heo S, Turner A, Lane WS, Chakravarti D (2001) Regulation of histone acetylation and transcription by INHAT, a human cellular complex containing the set oncoprotein. Cell 104: 119-130.
- Seo SB, Macfarlan T, McNamara P, Hong R, Mukai Y, Heo S, Chakravarti D (2002) Regulation of histone acetylation and transcription by nuclear protein pp32, a subunit of the INHAT complex. J Biol Chem 277: 14005-14010.
- Sharma GG, So S, Gupta A, Kumar R, Cayrou C, Avvakumov N, Bhadra U, Pandita RK, Porteus MH, Chen DJ, Cote J, Pandita TK (2010) MOF and histone H4 acetylation at lysine 16 are critical for DNA damage response and double-strand break repair. Mol Cell Biol 30: 3582-3595.
- Słomnicki LP, Leśniak W (2008) A putative role of the amyloid precursor protein intracellular domain (AICD) in transcription. Acta Neurobiol Exp (Wars) 68: 219-228.
- Sondag CM, Combs CK (2004) Amyloid precursor protein mediates proinflammatory activation of monocytic lineage cells. J Biol Chem 279: 14456-14463.
- Squatrito M, Gorrini C, Amati B (2006) Tip60 in DNA damage response and growth control: many tricks in one HAT. Trends Cell Biol 16: 433-442.
- Stante M, Minopoli G, Passaro F, Raia M, Vecchio LD, Russo T (2009) Fe65 is required for Tip60-directed histone H4 acetylation at DNA strand breaks. Proc Natl Acad Sci USA 106: 5093-5098.
- Sun Y, Xu Y, Roy K, Price BD (2007) DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity. Mol Cell Biol 27: 8502-8509.
- Sun Y, Jiang X, Xu Y, Ayrapetov MK, Moreau LA, Whetstine JR, Price BD (2009) Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60. Nat Cell Biol 11: 1376-1382.
- Sun Y, Jiang X, Price BD (2010) Tip60: connecting chromatin to DNA damage signaling. Cell Cycle 9: 930-936.
- Taipale M, Rea S, Richter K, Vilar A, Lichter P, Imhof A, Akhtar A (2005) hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells. Mol Cell Biol 25: 6798-6810.
- Tamayev R, Zhou D, D'Adamio L (2009) The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains. Mol Neurodegener 4: 28.
- Thomas T, Loveland KL, Voss AK (2007) The genes coding for the MYST family histone acetyltransferases, Tip60 and Mof, are expressed at high levels during sperm development. Gene Expr Patterns 7: 657-665.
- Thomas T, Dixon MP, Kueh AJ, Voss AK (2008) Mof (MYST1 or KAT8) is essential for progression of embryonic development past the blastocyst stage and required for normal chromatin architecture. Mol Cell Biol 28: 5093-5105.
- Telese F, Bruni P, Donizetti A, Gianni D, D'Ambrosio C, Scaloni A, Zambrano N, Rosenfeld MG, Russo T (2005) Transcription regulation by the adaptor protein Fe65 and the nucleosome assembly factor SET. EMBO Rep 6: 77-82.
- Varela I, Pereira S, Ugalde AP, Navarro CL, Suárez MF, Cau P, Cadiñanos J, Osorio FG, Foray N, Cobo J, de Carlos F, Lévy N, Freije JM, López-Otín C (2008) Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nat Med 14: 767-772.
- Vázquez MC, Vargas LM, Inestrosa NC, Alvarez AR (2009) c-Abl modulates AICD dependent cellular responses, transcriptional induction and apoptosis. J Cell Physiol 220: 136-143.
- von Rotz RC, Kohli BM, Bosset J, Meier M, Suzuki T, Nitsch RM, Konietzko U (2004) The APP intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor. J Cell Sci 117: 4435-4448.
- Williamson R, Scales T, Clark BR, Gibb G, Reynolds CH, Kellie S, Bird IN, Varndell IM, Sheppard PW, Everall I, Anderton BH (2002) Rapid tyrosine phosphorylation of neuronal proteins including tau and focal adhesion kinase in response to amyloid-beta peptide exposure, involvement of Src family protein kinases. J Neurosci 22: 10-20.
- Zambrano N, Minopoli G, de Candia P, Russo T (1998) The Fe65 adaptor protein interacts through its PID1 domain with the transcription factor CP2/LSF/LBP1. J Biol Chem 273: 20128-20133.
- Zarębski M, Wiernasz E, Dobrucki JW (2009) Recruitment of heterochromatin protein 1 to DNA repair sites. Cytometry A 75: 619-625