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CREBBP and p300 lysine acetyl transferases in the DNA damage response

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Abstract

The CREB-binding protein (CREBBP, or in short CBP) and p300 are lysine (K) acetyl transferases (KAT) belonging to the KAT3 family of proteins known to modify histones, as well as non-histone proteins, thereby regulating chromatin accessibility and transcription. Previous studies have indicated a tumor suppressor function for these enzymes. Recently, they have been found to acetylate key factors involved in DNA replication, and in different DNA repair processes, such as base excision repair, nucleotide excision repair, and non-homologous end joining. The growing list of CBP/p300 substrates now includes factors involved in DNA damage signaling, and in other pathways of the DNA damage response (DDR). This review will focus on the role of CBP and p300 in the acetylation of DDR proteins, and will discuss how this post-translational modification influences their functions at different levels, including catalytic activity, DNA binding, nuclear localization, and protein turnover. In addition, we will exemplify how these functions may be necessary to efficiently coordinate the spatio-temporal response to DNA damage. CBP and p300 may contribute to genome stability by fine-tuning the functions of DNA damage signaling and DNA repair factors, thereby expanding their role as tumor suppressors.

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References

  1. Bordoli L, Netsch M, Lüthi U, Lutz W, Eckner R (2001) Plant orthologs of p300/CBP: conservation of a core domain in metazoan p300/CBP acetyltransferase-related proteins. Nucleic Acids Res 29:589–597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Yuan LW, Giordano A (2002) Acetyltransferase machinery conserved in p300/CBP-family proteins. Oncogene 21:2253–2260

    Article  CAS  PubMed  Google Scholar 

  3. Goodman RH, Smolik S (2000) CBP/p300 in cell growth, transformation, and development. Genes Dev 14:1553–1577

    CAS  PubMed  Google Scholar 

  4. Kalkhoven E (2004) CBP and p300: HATs for different occasions. Biochem Pharmacol 68:1145–1155

    Article  CAS  PubMed  Google Scholar 

  5. Giordano A, Avantaggiati ML (1999) p300 and CBP: partners for life and death. J Cell Physiol 181:218–230

    Article  CAS  PubMed  Google Scholar 

  6. Chan HM, La Thangue NB (2001) p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J Cell Sci 114:2363–2373

    CAS  PubMed  Google Scholar 

  7. Bedford DC, Brindle PK (2012) Is histone acetylation the most important physiological function for CBP and p300? Aging 4:247–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dancy BM, Cole PA (2015) Protein lysine acetylation by p300/CBP. Chem Rev 115:2419–2452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang F, Marshall CB, Ikura M (2013) Transcriptional/epigenetic regulator CBP/p300 in tumorigenesis: structural and functional versatility in target recognition. Cell Mol Life Sci 70:3989–4008

    Article  CAS  PubMed  Google Scholar 

  10. Dyson HJ, Wright PE (2016) Role of intrinsic protein disorder in the function and interactions of the transcriptional coactivators CREB-binding protein (CBP) and p300. J Biol Chem 291:6714–6722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Delvecchio M, Gaucher J, Aguilar-Gurrieri C, Ortega E, Panne D (2013) Structure of the p300 catalytic core and implications for chromatin targeting and HAT regulation. Nat Struct Mol Biol 20:1040–1046

    Article  CAS  PubMed  Google Scholar 

  12. Yao TP, Oh SP, Fuchs M, Zhou ND, Ch’ng LE, Newsome D, Bronson RT, Li E, Livingston DM, Eckner R (1998) Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93:361–372

    Article  CAS  PubMed  Google Scholar 

  13. Tanaka Y, Naruse I, Maekawa T, Masuya H, Shiroishi T, Ishii S (1997) Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein–Taybi syndrome. Proc Natl Acad Sci USA 94:10215–10220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gayther SA, Batley SJ, Linger L, Bannister A, Thorpe K, Chin SF, Daigo Y, Russell P, Wilson A, Sowter HM, Delhanty JD, Ponder BA, Kouzarides T, Caldas C (2000) Mutations truncating the EP300 acetylase in human cancers. Nat Genet 24:300–303

    Article  CAS  PubMed  Google Scholar 

  15. Iyer NG, Ozdag H, Caldas C (2004) p300/CBP and cancer. Oncogene 23:4225–4231

    Article  CAS  PubMed  Google Scholar 

  16. Dutta R, Tiu B, Sakamoto KM (2016) CBP/p300 acetyltransferase activity in hematologic malignancies. Mol Genet Metab 119:37–43

    Article  CAS  PubMed  Google Scholar 

  17. Giles RH, Peters DJ, Breuning MH (1998) Conjunction dysfunction: CBP/p300 in human disease. Trends Genet 14:178–183

    Article  CAS  PubMed  Google Scholar 

  18. Kung AL, Rebel VI, Bronson RT, Ch’ng LE, Sieff CA, Livingston DM, Yao TP (2000) Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP. Genes Dev 14:272–277

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Attar N, Kurdistani SK (2017) Exploitation of EP300 and CREBBP lysine acetyltransferases by cancer. Cold Spring Harb Perspect Med. https://doi.org/10.1101/cshperspect

    PubMed  Google Scholar 

  20. Grossman SR (2001) p300/CBP/p53 interaction and regulation of the p53 response. Eur J Biochem 268:2773–2778

    Article  CAS  PubMed  Google Scholar 

  21. Dai C, Gu W (2010) p53 post-translational modification: deregulated in tumorigenesis. Trends Mol Med 16:528–536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Reed SM, Quelle DE (2014) p53 acetylation: regulation and consequences. Cancers 7:30–69

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ogiwara H, Kohno T (2012) CBP and p300 histone acetyltransferases contribute to homologous recombination by transcriptionally activating the BRCA1 and RAD51 genes. PLoS One 7:e52810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ogiwara H, Ui A, Otsuka A, Satoh H, Yokomi I, Nakajima S, Yasui A, Yokota J, Kohno T (2011) Histone acetylation by CBP and p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors. Oncogene 30:2135–2146

    Article  CAS  PubMed  Google Scholar 

  25. Li S (2012) Implication of posttranslational histone modifications in nucleotide excision repair. Int J Mol Sci 13:12461–12486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gong F, Miller KM (2013) Mammalian DNA repair: HATs and HDACs make their mark through histone acetylation. Mutat Res 750:23–30

    Article  CAS  PubMed  Google Scholar 

  27. Hasan S, Hottiger MO (2002) Histone acetyl transferases: a role in DNA repair and DNA replication. J Mol Med 80:463–474

    Article  CAS  PubMed  Google Scholar 

  28. Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40:179–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325:834–840

    Article  CAS  PubMed  Google Scholar 

  30. Averbeck NB, Durante M (2011) Protein acetylation within the cellular response to radiation. J Cell Physiol 226:962–967

    Article  CAS  PubMed  Google Scholar 

  31. Bennetzen MV, Larsen DH, Dinant C, Watanabe S, Bartek J, Lukas J, Andersen JS (2013) Acetylation dynamics of human nuclear proteins during the ionizing radiation-induced DNA damage response. Cell Cycle 12:1688–1695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Li M, Yu X (2015) The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy. Oncogene 34:3349–3356

    Article  CAS  PubMed  Google Scholar 

  33. Kim MY, Mauro S, Gévry N, Lis JT, Kraus WL (2004) NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1. Cell 119:803–814

    Article  CAS  PubMed  Google Scholar 

  34. Aredia F, Scovassi AI (2014) Poly(ADP-ribose): a signaling molecule in different paradigms of cell death. Biochem Pharmacol 92:157–163

    Article  CAS  PubMed  Google Scholar 

  35. Hassa PO, Haenni SS, Buerki C, Meier NI, Lane WS, Owen H, Gersbach M, Imhof R, Hottiger MO (2005) Acetylation of poly(ADP-ribose) polymerase-1 by p300/CREB binding protein regulates coactivation of NF-κB-dependent transcription. J Biol Chem 280:40450–40464

    Article  CAS  PubMed  Google Scholar 

  36. Messner S, Schuermann D, Altmeyer M, Kassner I, Schmidt D, Schär P, Müller S, Hottiger MO (2009) Sumoylation of poly(ADP-ribose) polymerase 1 inhibits its acetylation and restrains transcriptional coactivator function. FASEB J 23:3978–3989

    Article  CAS  PubMed  Google Scholar 

  37. Altmeyer M, Messner S, Hassa PO, Fey M, Hottiger MO (2009) Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites. Nucleic Acids Res 37:3723–3738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Robert C, Nagaria PK, Pawar N, Adewuyi A, Gojo I, Meyers DJ, Cole PA, Rassool FV (2016) Histone deacetylase inhibitors decrease NHEJ both by acetylation of repair factors and trapping of PARP1 at DNA double-strand breaks in chromatin. Leuk Res 45:14–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Jiang X, Xu Y, Price BD (2010) Acetylation of H2AX on lysine 36 plays a key role in the DNA double-strand break repair pathway. FEBS Lett 584:2926–2930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jang ER, Choi JD, Lee JS (2011) Acetyltransferase p300 regulates NBS1-mediated DNA damage response. FEBS Lett 585:47–52

    Article  CAS  PubMed  Google Scholar 

  41. Richard DJ, Bolderson E, Cubeddu L, Wadsworth RI, Savage K, Sharma GG, Nicolette ML, Tsvetanov S, McIlwraith MJ, Pandita RK, Takeda S, Hay RT, Gautier J, West SC, Paull TT, Pandita TK, White MF, Khanna KK (2008) Single-stranded DNA-binding protein hSSB1 is critical for genomic stability. Nature 453:677–681

    Article  CAS  PubMed  Google Scholar 

  42. Xu S, Wu Y, Chen Q, Cao J, Hu K, Tang J, Sang Y, Lai F, Wang L, Zhang R, Li SP, Zeng YX, Yin Y, Kang T (2013) hSSB1 regulates both the stability and the transcriptional activity of p53. Cell Res 23:423–435

    Article  CAS  PubMed  Google Scholar 

  43. Wu Y, Chen H, Lu J, Zhang M, Zhang R, Duan T, Wang X, Huang J, Kang T (2015) Acetylation-dependent function of human single-stranded DNA binding protein 1. Nucleic Acids Res 43:7878–7887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Moldovan GL, Pfander B, Jentsch S (2007) PCNA, the maestro of the replication fork. Cell 129:665–679

    Article  CAS  PubMed  Google Scholar 

  45. Hasan S, Hassa PO, Imhof R, Hottiger MO (2001) Transcription coactivator p300 binds PCNA and may have a role in DNA repair synthesis. Nature 410:387–391

    Article  CAS  PubMed  Google Scholar 

  46. Naryzhny SN, Lee H (2004) The post-translational modifications of proliferating cell nuclear antigen: acetylation, not phosphorylation, plays an important role in the regulation of its function. J Biol Chem 279:20194–20199

    Article  CAS  PubMed  Google Scholar 

  47. Yu Y, Cai JP, Tu B, Wu L, Zhao Y, Liu X, Li L, McNutt MA, Feng J, He Q, Yang Y, Wang H, Sekiguchi M, Zhu WG (2009) Proliferating cell nuclear antigen is protected from degradation by forming a complex with MutT Homolog2. J Biol Chem 284:19310–19320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cazzalini O, Sommatis S, Tillhon M, Dutto I, Bachi A, Rapp A, Nardo T, Scovassi AI, Necchi D, Cardoso MC, Stivala LA, Prosperi E (2014) CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis. Nucleic Acids Res 42:8433–8448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Georgescu RE, Kim SS, Yurieva O, Kuriyan J, Kong XP, O’Donnell M (2008) Structure of a sliding clamp on DNA. Cell 132:43–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Burgers PMJ, Kunkel TA (2017) Eukaryotic DNA replication fork. Ann Rev Biochem 86:417–438

    Article  CAS  PubMed  Google Scholar 

  51. Hasan S, Stucki M, Hassa PO, Imhof R, Gehrig P, Hunziker P, Hübscher U, Hottiger MO (2001) Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300. Mol Cell 7:1221–1231

    Article  CAS  PubMed  Google Scholar 

  52. Friedrich-Heineken E, Henneke G, Ferrari E, Hübscher U (2003) The acetylatable lysines of human Fen1 are important for endo- and exonuclease activities. J Mol Biol 328:73–84

    Article  CAS  PubMed  Google Scholar 

  53. Balakrishnan L, Stewart J, Polaczek P, Campbell JL, Bambara RA (2010) Acetylation of Dna2 endonuclease/helicase and flap endonuclease 1 by p300 promotes DNA stability by creating long flap intermediates. J Biol Chem 285:4398–4404

    Article  CAS  PubMed  Google Scholar 

  54. Krokan HE, Sætrom P, Aas PA, Pettersen HS, Kavli B, Slupphaug G (2014) Error-free versus mutagenic processing of genomic uracil—relevance to cancer. DNA Repair 19:38–47

    Article  CAS  PubMed  Google Scholar 

  55. Bellacosa A, Drohat AC (2015) Role of base excision repair in maintaining the genetic and epigenetic integrity of CpG sites. DNA Repair 32:33–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Tini M, Benecke A, Um SJ, Torchia J, Evans RM, Chambon P (2002) Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription. Mol Cell 9:265–277

    Article  CAS  PubMed  Google Scholar 

  57. Mohan RD, Litchfield DW, Torchia J, Tini M (2010) Opposing regulatory roles of phosphorylation and acetylation in DNA mispair processing by thymine DNA glycosylase. Nucleic Acids Res 38:1135–1148

    Article  CAS  PubMed  Google Scholar 

  58. Dutta A, Yang C, Sengupta S, Mitra S, Hegde ML (2015) New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins. Cell Mol Life Sci 72:1679–1698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Bhakat KK, Mokkapati SK, Boldogh I, Hazra TK, Mitra S (2006) Acetylation of human 8-oxoguanine-DNA glycosylase by p300 and its role in 8-oxoguanine repair in vivo. Mol Cell Biol 26:1654–1665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Radak Z, Bori Z, Koltai E, Fatouros IG, Jamurtas AZ, Douroudos II, Terzis G, Nikolaidis MG, Chatzinikolaou A, Sovatzidis A, Kumagai S, Naito H, Boldogh I (2011) Age-dependent changes in 8-oxoguanine-DNA glycosylase activity are modulated by adaptive responses to physical exercise in human skeletal muscle. Free Radic Biol Med 51:417–423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kang L, Zhao W, Zhang G, Wu J, Guan H (2015) Acetylated 8-oxoguanine DNA glycosylase 1 and its relationship with p300 and SIRT1 in lens epithelium cells from age-related cataract. Exp Eye Res 135:102–108

    Article  CAS  PubMed  Google Scholar 

  62. Cheng Y, Ren X, Gowda AS, Shan Y, Zhang L, Yuan YS, Patel R, Wu H, Huber-Keener K, Yang JW, Liu D, Spratt TE, Yang JM (2013) Interaction of Sirt3 with OGG1 contributes to repair of mitochondrial DNA and protects from apoptotic cell death under oxidative stress. Cell Death Dis 18:e731

    Article  CAS  Google Scholar 

  63. Bhakat KK, Hazra TK, Mitra S (2004) Acetylation of the human DNA glycosylase NEIL2 and inhibition of its activity. Nucleic Acids Res 32:3033–3039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Likhite VS, Cass EI, Anderson SD, Yates JR, Nardulli AM (2004) Interaction of estrogen receptor alpha with 3-methyladenine DNA glycosylase modulates transcription and DNA repair. J Biol Chem 279:16875–16882

    Article  CAS  PubMed  Google Scholar 

  65. Bhakat KK, Izumi T, Yang SH, Hazra TK, Mitra S (2003) Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene. EMBO J 22:6299–6309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Sengupta S, Mantha AK, Mitra S, Bhakat KK (2011) Human AP endonuclease (APE1/Ref-1) and its acetylation regulate YB-1-p300 recruitment and RNA polymerase II loading in the drug-induced activation of multidrug resistance gene MDR1. Oncogene 30:482–493

    Article  CAS  PubMed  Google Scholar 

  67. Busso CS, Lake MW, Izumi T (2010) Posttranslational modification of mammalian AP endonuclease (APE1). Cell Mol Life Sci 67:3609–3620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Fantini D, Vascotto C, Marasco D, D’Ambrosio C, Romanello M, Vitagliano L, Pedone C, Poletto M, Cesaratto L, Quadrifoglio F, Scaloni A, Radicella JP, Tell G (2010) Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions. Nucleic Acids Res 38:8239–8256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Lirussi L, Antoniali G, Vascotto C, D’Ambrosio C, Poletto M, Romanello M, Marasco D, Leone M, Quadrifoglio F, Bhakat KK, Scaloni A, Tell G (2012) Nucleolar accumulation of APE1 depends on charged lysine residues that undergo acetylation upon genotoxic stress and modulate its BER activity in cells. Mol Biol Cell 23:4079–4096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Roychoudhury S, Nath S, Song H, Hegde ML, Bellot LJ, Mantha AK, Sengupta S, Ray S, Natarajan A, Bhakat KK (2017) Human apurinic/apyrimidinic endonuclease (APE1) is acetylated at DNA damage sites in chromatin, and acetylation modulates its DNA repair activity. Mol Cell Biol. https://doi.org/10.1128/MCB.00401-16

    PubMed  PubMed Central  Google Scholar 

  71. Sengupta S, Mantha AK, Song H, Roychoudhury S, Nath S, Ray S, Bhakat KK (2016) Elevated level of acetylation of APE1 in tumor cells modulates DNA damage repair. Oncotarget 7:75197–75209

    Article  PubMed  PubMed Central  Google Scholar 

  72. Bhakat KK, Sengupta S, Adeniyi VF, Roychoudhury S, Nath S, Bellot LJ, Feng D, Mantha AK, Sinha M, Qiu S, Luxon BA (2016) Regulation of limited N-terminal proteolysis of APE1 in tumor via acetylation and its role in cell proliferation. Oncotarget 7:22590–22604

    Article  PubMed  PubMed Central  Google Scholar 

  73. Yamamori T, DeRicco J, Naqvi A, Hoffman TA, Mattagajasingh I, Kasuno K, Jung SB, Kim CS, Irani K (2010) SIRT1 deacetylates APE1 and regulates cellular base excision repair. Nucleic Acids Res 38:832–845

    Article  CAS  PubMed  Google Scholar 

  74. Goellner EM, Svilar D, Almeida KH, Sobol RW (2012) Targeting DNA polymerase β for therapeutic intervention. Curr Mol Pharmacol 5:68–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Simonelli V, Mazzei F, D’Errico M, Dogliotti E (2012) Gene susceptibility to oxidative damage: from single nucleotide polymorphisms to function. Mutat Res 731:1–13

    Article  CAS  PubMed  Google Scholar 

  76. Hasan S, El-Andaloussi N, Hardeland U, Hassa PO, Bürki C, Imhof R, Schär P, Hottiger MO (2002) Acetylation regulates the DNA end-trimming activity of DNA polymerase β. Mol Cell 10:1213–1222

    Article  CAS  PubMed  Google Scholar 

  77. Balliano A, Hao F, Njeri C, Balakrishnan L, Hayes JJ (2017) HMGB1 stimulates activity of polymerase β on nucleosome substrates. Biochemistry 56:647–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Zhu Q, Wani AA (2017) Nucleotide excision repair: finely tuned molecular orchestra of early pre-incision events. Photochem Photobiol 93:166–177

    Article  CAS  PubMed  Google Scholar 

  79. Datta A, Bagchi S, Nag A, Shiyanov P, Adami GR, Yoon T, Raychaudhuri P (2001) The p48 subunit of the damaged-DNA binding protein DDB associates with the CBP/p300 family of histone acetyltransferase. Mutat Res 486:89–97

    Article  CAS  PubMed  Google Scholar 

  80. Rapic-Otrin V, McLenigan MP, Bisi DC, Gonzalez M, Levine AS (2002) Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation. Nucleic Acids Res 30:2588–2598

    Article  CAS  PubMed  Google Scholar 

  81. Marteijn JA, Lans H, Vermeulen W, Hoeijmakers JH (2014) Understanding nucleotide excision repair and its roles in cancer and ageing. Nat Rev Mol Cell Biol 15:465–481

    Article  CAS  PubMed  Google Scholar 

  82. Fan W, Luo J (2010) SIRT1 regulates UV-induced DNA repair through deacetylating XPA. Mol Cell 39:247–258

    Article  CAS  PubMed  Google Scholar 

  83. Kang TH, Reardon JT, Sancar A (2011) Regulation of nucleotide excision repair activity by transcriptional and post-transcriptional control of the XPA protein. Nucleic Acids Res 39:3176–3187

    Article  CAS  PubMed  Google Scholar 

  84. Tillhon M, Cazzalini O, Nardo T, Necchi D, Sommatis S, Stivala LA, Scovassi AI, Prosperi E (2012) p300/CBP acetyl transferases interact with and acetylate the nucleotide excision repair factor XPG. DNA Repair 11:844–852

    Article  CAS  PubMed  Google Scholar 

  85. Hong R, Chakravarti D (2003) The human proliferating cell nuclear antigen regulates transcription coactivator p300 activity and promotes transcriptional repression. J Biol Chem 278:44505–44513

    Article  CAS  PubMed  Google Scholar 

  86. Cazzalini O, Perucca P, Savio M, Necchi D, Bianchi L, Stivala LA, Ducommun B, Scovassi AI, Prosperi E (2008) Interaction of p21CDKN1A with PCNA regulates the histone acetyltransferase activity of p300 in nucleotide excision repair. Nucleic Acids Res 36:1713–1722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Cohen HY, Lavu S, Bitterman KJ, Hekking B, Imahiyerobo TA, Miller C, Frye R, Ploegh H, Kessler BM, Sinclair DA (2004) Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis. Mol Cell 13:627–638

    Article  CAS  PubMed  Google Scholar 

  88. Chen CS, Wang YC, Yang HC, Huang PH, Kulp SK, Yang CC, Lu YS, Matsuyama S, Chen CY, Chen CS (2007) Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku70 acetylation. Cancer Res 67:5318–5327

    Article  CAS  PubMed  Google Scholar 

  89. Subramanian C, Hada M, Opipari AW Jr, Castle VP, Kwok RP (2013) CREB-binding protein regulates Ku70 acetylation in response to ionization radiation in neuroblastoma. Mol Cancer Res 11:173–181

    Article  CAS  PubMed  Google Scholar 

  90. Croteau DL, Popuri V, Opresko PL, Bohr VA (2014) Human RecQ helicases in DNA repair, recombination, and replication. Annu Rev Biochem 83:519–552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Pichierri P, Ammazzalorso F, Bignami M, Franchitto A (2011) The Werner syndrome protein: linking the replication checkpoint response to genome stability. Aging 3:311–318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Blander G, Zalle N, Daniely Y, Taplick J, Gray MD, Oren M (2002) DNA damage-induced translocation of the Werner helicase is regulated by acetylation. J Biol Chem 277:50934–50940

    Article  CAS  PubMed  Google Scholar 

  93. Muftuoglu M, Kusumoto R, Speina E, Beck G, Cheng WH, Bohr VA (2008) Acetylation regulates WRN catalytic activities and affects base excision DNA repair. PLoS One 3:e1918

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Lozada E, Yi J, Luo J, Orren DK (2014) Acetylation of Werner syndrome protein (WRN): relationships with DNA damage, DNA replication and DNA metabolic activities. Biogerontology 15:347–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Li K, Wang R, Lozada E, Fan W, Orren DK, Luo J (2010) Acetylation of WRN protein regulates its stability by inhibiting ubiquitination. PLoS One 5:e10341

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Dietschy T, Shevelev I, Pena-Diaz J, Hühn D, Kuenzle S, Mak R, Miah MF, Hess D, Fey M, Hottiger MO, Janscak P, Stagljar I (2009) p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization. J Cell Sci 122:1258–1267

    Article  CAS  PubMed  Google Scholar 

  97. Wu Y, Suhasini AN, Brosh RM Jr (2009) Welcome the family of FANCJ-like helicases to the block of genome stability maintenance proteins. Cell Mol Life Sci 66:1209–1222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Xie J, Peng M, Guillemette S, Quan S, Maniatis S, Wu Y, Venkatesh A, Shaffer SA, Brosh RM Jr, Cantor SB (2012) FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA damage response. PLoS Genet 8:e1002786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Lukas J, Lukas C, Bartek J (2011) More than just a focus: the chromatin response to DNA damage and its role in genome integrity maintenance. Nat Cell Biol 13:1161–1169

    Article  CAS  PubMed  Google Scholar 

  100. Stauffer D, Chang B, Huang J, Dunn A, Thayer M (2007) p300/CREB-binding protein interacts with ATR and is required for the DNA replication checkpoint. J Biol Chem 282:9678–9687

    Article  CAS  PubMed  Google Scholar 

  101. Larsen DH, Poinsignon C, Gudjonsson T, Dinant C, Payne MR, Hari FJ, Rendtlew Danielsen JM, Menard P, Sand JC, Stucki M, Lukas C, Bartek J, Andersen JS, Lukas J (2010) The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage. J Cell Biol 190:731–740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Polo SE, Kaidi A, Baskcomb L, Galanty Y, Jackson SP (2010) Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4. EMBO J 29:3130–3139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Qi W, Chen H, Xiao T, Wang R, Li T, Han L, Zeng X (2016) Acetyltransferase p300 collaborates with chromodomain helicase DNA-binding protein 4 (CHD4) to facilitate DNA double-strand break repair. Mutagenesis 31:193–203

    Article  CAS  PubMed  Google Scholar 

  104. Piekna-Przybylska D, Bambara RA, Balakrishnan L (2016) Acetylation regulates DNA repair mechanisms in human cells. Cell Cycle 15:1506–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Bjoras KO, Sousa MML, Sharma A, Fonseca DM, Sogaard CK, Bjoras M, Otterlei M (2017) Monitoring of the spatial and temporal dynamics of BER/SSBR pathway proteins, including MYH, UNG2, MPG, NTH1 and NEIL1-3, during DNA replication. Nucleic Acids Res 45:8291–8301

    Article  CAS  Google Scholar 

  106. Carter RJ, Parsons JL (2016) Base excision repair, a pathway regulated by posttranslational modifications. Mol Cell Biol 36:1426–1437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Puumalainen MR, Lessel D, Rüthemann P, Kaczmarek N, Bachmann K, Ramadan K, Naegeli H (2014) Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity. Nat Commun. https://doi.org/10.1038/ncomms4695

    PubMed  PubMed Central  Google Scholar 

  108. van Cuijk L, van Belle GJ, Turkyilmaz Y, Poulsen SL, Janssens RC, Theil AF, Sabatella M, Lans H, Mailand N, Houtsmuller AB, Vermeulen W, Marteijn JA (2015) SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair. Nat Commun. https://doi.org/10.1038/ncomms8499

    PubMed  PubMed Central  Google Scholar 

  109. Sadoul K, Boyault C, Pabion M, Khochbin S (2008) Regulation of protein turnover by acetyltransferases and deacetylases. Biochimie 90:306–312

    Article  CAS  PubMed  Google Scholar 

  110. Zimmer SN, Lemieux ME, Karia BP, Day C, Zhou T, Zhou Q, Kung AL, Suresh U, Chen Y, Kinney MC, Bishop AJ, Rebel VI (2012) Mice heterozygous for CREB binding protein are hypersensitive to γ-radiation and invariably develop myelodysplastic/myeloproliferative neoplasm. Exp Hematol 40:295–306

    Article  CAS  PubMed  Google Scholar 

  111. Wang QE, Han C, Zhao R, Wani G, Zhu Q, Gong L, Battu A, Racoma I, Sharma N, Wani AA (2013) p38 MAPK- and Akt-mediated p300 phosphorylation regulates its degradation to facilitate nucleotide excision repair. Nucleic Acids Res 41:1722–1733

    Article  CAS  PubMed  Google Scholar 

  112. Yan G, Eller MS, Elm C, Larocca CA, Ryu B, Panova IP, Dancy BM, Bowers EM, Meyers D, Lareau L, Cole PA, Taverna SD, Alani RM (2013) Selective inhibition of p300 HAT blocks cell cycle progression, induces cellular senescence, and inhibits the DNA damage response in melanoma cells. J Investig Dermatol 133:2444–2452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work is funded by “Associazione Italiana per la Ricerca sul Cancro”, IG Grant 17041 to E.P.

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  1. Ilaria Dutto

    Present address: IRB, Carrer Baldiri Reixac 10, 08028, Barcelona, Spain

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  1. Istituto di Genetica Molecolare del CNR, Via Abbiategrasso 207, 27100, Pavia, Italy

    Ilaria Dutto, Claudia Scalera & Ennio Prosperi

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  1. Ilaria Dutto
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  2. Claudia Scalera
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  3. Ennio Prosperi
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Correspondence to Ennio Prosperi.

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Dutto, I., Scalera, C. & Prosperi, E. CREBBP and p300 lysine acetyl transferases in the DNA damage response. Cell. Mol. Life Sci. 75, 1325–1338 (2018). https://doi.org/10.1007/s00018-017-2717-4

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  • DOI: https://doi.org/10.1007/s00018-017-2717-4

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