Cellular and Molecular Life Sciences

, Volume 75, Issue 8, pp 1325–1338 | Cite as

CREBBP and p300 lysine acetyl transferases in the DNA damage response

  • Ilaria Dutto
  • Claudia Scalera
  • Ennio Prosperi


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.


DNA repair DNA replication DNA repair enzymes Protein acetylation Post-translational modification 



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


  1. 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 29:589–597PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Yuan LW, Giordano A (2002) Acetyltransferase machinery conserved in p300/CBP-family proteins. Oncogene 21:2253–2260PubMedCrossRefGoogle Scholar
  3. 3.
    Goodman RH, Smolik S (2000) CBP/p300 in cell growth, transformation, and development. Genes Dev 14:1553–1577PubMedGoogle Scholar
  4. 4.
    Kalkhoven E (2004) CBP and p300: HATs for different occasions. Biochem Pharmacol 68:1145–1155PubMedCrossRefGoogle Scholar
  5. 5.
    Giordano A, Avantaggiati ML (1999) p300 and CBP: partners for life and death. J Cell Physiol 181:218–230PubMedCrossRefGoogle Scholar
  6. 6.
    Chan HM, La Thangue NB (2001) p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J Cell Sci 114:2363–2373PubMedGoogle Scholar
  7. 7.
    Bedford DC, Brindle PK (2012) Is histone acetylation the most important physiological function for CBP and p300? Aging 4:247–255PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Dancy BM, Cole PA (2015) Protein lysine acetylation by p300/CBP. Chem Rev 115:2419–2452PubMedPubMedCentralCrossRefGoogle Scholar
  9. 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 70:3989–4008PubMedCrossRefGoogle Scholar
  10. 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 291:6714–6722PubMedPubMedCentralCrossRefGoogle Scholar
  11. 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 20:1040–1046PubMedCrossRefGoogle Scholar
  12. 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 93:361–372PubMedCrossRefGoogle Scholar
  13. 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 94:10215–10220PubMedPubMedCentralCrossRefGoogle Scholar
  14. 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 24:300–303PubMedCrossRefGoogle Scholar
  15. 15.
    Iyer NG, Ozdag H, Caldas C (2004) p300/CBP and cancer. Oncogene 23:4225–4231PubMedCrossRefGoogle Scholar
  16. 16.
    Dutta R, Tiu B, Sakamoto KM (2016) CBP/p300 acetyltransferase activity in hematologic malignancies. Mol Genet Metab 119:37–43PubMedCrossRefGoogle Scholar
  17. 17.
    Giles RH, Peters DJ, Breuning MH (1998) Conjunction dysfunction: CBP/p300 in human disease. Trends Genet 14:178–183PubMedCrossRefGoogle Scholar
  18. 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 14:272–277PubMedPubMedCentralGoogle Scholar
  19. 19.
    Attar N, Kurdistani SK (2017) Exploitation of EP300 and CREBBP lysine acetyltransferases by cancer. Cold Spring Harb Perspect Med. PubMedGoogle Scholar
  20. 20.
    Grossman SR (2001) p300/CBP/p53 interaction and regulation of the p53 response. Eur J Biochem 268:2773–2778PubMedCrossRefGoogle Scholar
  21. 21.
    Dai C, Gu W (2010) p53 post-translational modification: deregulated in tumorigenesis. Trends Mol Med 16:528–536PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Reed SM, Quelle DE (2014) p53 acetylation: regulation and consequences. Cancers 7:30–69PubMedPubMedCentralCrossRefGoogle Scholar
  23. 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:e52810PubMedPubMedCentralCrossRefGoogle Scholar
  24. 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 30:2135–2146PubMedCrossRefGoogle Scholar
  25. 25.
    Li S (2012) Implication of posttranslational histone modifications in nucleotide excision repair. Int J Mol Sci 13:12461–12486PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Gong F, Miller KM (2013) Mammalian DNA repair: HATs and HDACs make their mark through histone acetylation. Mutat Res 750:23–30PubMedCrossRefGoogle Scholar
  27. 27.
    Hasan S, Hottiger MO (2002) Histone acetyl transferases: a role in DNA repair and DNA replication. J Mol Med 80:463–474PubMedCrossRefGoogle Scholar
  28. 28.
    Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40:179–204PubMedPubMedCentralCrossRefGoogle Scholar
  29. 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 325:834–840PubMedCrossRefGoogle Scholar
  30. 30.
    Averbeck NB, Durante M (2011) Protein acetylation within the cellular response to radiation. J Cell Physiol 226:962–967PubMedCrossRefGoogle Scholar
  31. 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 12:1688–1695PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Li M, Yu X (2015) The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy. Oncogene 34:3349–3356PubMedCrossRefGoogle Scholar
  33. 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 119:803–814PubMedCrossRefGoogle Scholar
  34. 34.
    Aredia F, Scovassi AI (2014) Poly(ADP-ribose): a signaling molecule in different paradigms of cell death. Biochem Pharmacol 92:157–163PubMedCrossRefGoogle Scholar
  35. 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 280:40450–40464PubMedCrossRefGoogle Scholar
  36. 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 23:3978–3989PubMedCrossRefGoogle Scholar
  37. 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 37:3723–3738PubMedPubMedCentralCrossRefGoogle Scholar
  38. 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 45:14–23PubMedPubMedCentralCrossRefGoogle Scholar
  39. 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 584:2926–2930PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Jang ER, Choi JD, Lee JS (2011) Acetyltransferase p300 regulates NBS1-mediated DNA damage response. FEBS Lett 585:47–52PubMedCrossRefGoogle Scholar
  41. 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 453:677–681PubMedCrossRefGoogle Scholar
  42. 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 23:423–435PubMedCrossRefGoogle Scholar
  43. 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 43:7878–7887PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Moldovan GL, Pfander B, Jentsch S (2007) PCNA, the maestro of the replication fork. Cell 129:665–679PubMedCrossRefGoogle Scholar
  45. 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 410:387–391PubMedCrossRefGoogle Scholar
  46. 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 279:20194–20199PubMedCrossRefGoogle Scholar
  47. 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 284:19310–19320PubMedPubMedCentralCrossRefGoogle Scholar
  48. 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 42:8433–8448PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Georgescu RE, Kim SS, Yurieva O, Kuriyan J, Kong XP, O’Donnell M (2008) Structure of a sliding clamp on DNA. Cell 132:43–54PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Burgers PMJ, Kunkel TA (2017) Eukaryotic DNA replication fork. Ann Rev Biochem 86:417–438PubMedCrossRefGoogle Scholar
  51. 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 7:1221–1231PubMedCrossRefGoogle Scholar
  52. 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 328:73–84PubMedCrossRefGoogle Scholar
  53. 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 285:4398–4404PubMedCrossRefGoogle Scholar
  54. 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 19:38–47PubMedCrossRefGoogle Scholar
  55. 55.
    Bellacosa A, Drohat AC (2015) Role of base excision repair in maintaining the genetic and epigenetic integrity of CpG sites. DNA Repair 32:33–42PubMedPubMedCentralCrossRefGoogle Scholar
  56. 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 9:265–277PubMedCrossRefGoogle Scholar
  57. 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 38:1135–1148PubMedCrossRefGoogle Scholar
  58. 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 72:1679–1698PubMedPubMedCentralCrossRefGoogle Scholar
  59. 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 26:1654–1665PubMedPubMedCentralCrossRefGoogle Scholar
  60. 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 51:417–423PubMedPubMedCentralCrossRefGoogle Scholar
  61. 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 135:102–108PubMedCrossRefGoogle Scholar
  62. 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:e731CrossRefGoogle Scholar
  63. 63.
    Bhakat KK, Hazra TK, Mitra S (2004) Acetylation of the human DNA glycosylase NEIL2 and inhibition of its activity. Nucleic Acids Res 32:3033–3039PubMedPubMedCentralCrossRefGoogle Scholar
  64. 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 279:16875–16882PubMedCrossRefGoogle Scholar
  65. 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 22:6299–6309PubMedPubMedCentralCrossRefGoogle Scholar
  66. 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 30:482–493PubMedCrossRefGoogle Scholar
  67. 67.
    Busso CS, Lake MW, Izumi T (2010) Posttranslational modification of mammalian AP endonuclease (APE1). Cell Mol Life Sci 67:3609–3620PubMedPubMedCentralCrossRefGoogle Scholar
  68. 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 38:8239–8256PubMedPubMedCentralCrossRefGoogle Scholar
  69. 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 23:4079–4096PubMedPubMedCentralCrossRefGoogle Scholar
  70. 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. PubMedPubMedCentralGoogle Scholar
  71. 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 7:75197–75209PubMedPubMedCentralCrossRefGoogle Scholar
  72. 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 7:22590–22604PubMedPubMedCentralCrossRefGoogle Scholar
  73. 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 38:832–845PubMedCrossRefGoogle Scholar
  74. 74.
    Goellner EM, Svilar D, Almeida KH, Sobol RW (2012) Targeting DNA polymerase β for therapeutic intervention. Curr Mol Pharmacol 5:68–87PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Simonelli V, Mazzei F, D’Errico M, Dogliotti E (2012) Gene susceptibility to oxidative damage: from single nucleotide polymorphisms to function. Mutat Res 731:1–13PubMedCrossRefGoogle Scholar
  76. 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 10:1213–1222PubMedCrossRefGoogle Scholar
  77. 77.
    Balliano A, Hao F, Njeri C, Balakrishnan L, Hayes JJ (2017) HMGB1 stimulates activity of polymerase β on nucleosome substrates. Biochemistry 56:647–656PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Zhu Q, Wani AA (2017) Nucleotide excision repair: finely tuned molecular orchestra of early pre-incision events. Photochem Photobiol 93:166–177PubMedCrossRefGoogle Scholar
  79. 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 486:89–97PubMedCrossRefGoogle Scholar
  80. 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 30:2588–2598PubMedCrossRefGoogle Scholar
  81. 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 15:465–481PubMedCrossRefGoogle Scholar
  82. 82.
    Fan W, Luo J (2010) SIRT1 regulates UV-induced DNA repair through deacetylating XPA. Mol Cell 39:247–258PubMedCrossRefGoogle Scholar
  83. 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 39:3176–3187PubMedCrossRefGoogle Scholar
  84. 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 11:844–852PubMedCrossRefGoogle Scholar
  85. 85.
    Hong R, Chakravarti D (2003) The human proliferating cell nuclear antigen regulates transcription coactivator p300 activity and promotes transcriptional repression. J Biol Chem 278:44505–44513PubMedCrossRefGoogle Scholar
  86. 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 36:1713–1722PubMedPubMedCentralCrossRefGoogle Scholar
  87. 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 13:627–638PubMedCrossRefGoogle Scholar
  88. 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 67:5318–5327PubMedCrossRefGoogle Scholar
  89. 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 11:173–181PubMedCrossRefGoogle Scholar
  90. 90.
    Croteau DL, Popuri V, Opresko PL, Bohr VA (2014) Human RecQ helicases in DNA repair, recombination, and replication. Annu Rev Biochem 83:519–552PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Pichierri P, Ammazzalorso F, Bignami M, Franchitto A (2011) The Werner syndrome protein: linking the replication checkpoint response to genome stability. Aging 3:311–318PubMedPubMedCentralCrossRefGoogle Scholar
  92. 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 277:50934–50940PubMedCrossRefGoogle Scholar
  93. 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:e1918PubMedPubMedCentralCrossRefGoogle Scholar
  94. 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 15:347–366PubMedPubMedCentralCrossRefGoogle Scholar
  95. 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:e10341PubMedPubMedCentralCrossRefGoogle Scholar
  96. 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 122:1258–1267PubMedCrossRefGoogle Scholar
  97. 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 66:1209–1222PubMedPubMedCentralCrossRefGoogle Scholar
  98. 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:e1002786PubMedPubMedCentralCrossRefGoogle Scholar
  99. 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 13:1161–1169PubMedCrossRefGoogle Scholar
  100. 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 282:9678–9687PubMedCrossRefGoogle Scholar
  101. 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 190:731–740PubMedPubMedCentralCrossRefGoogle Scholar
  102. 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 29:3130–3139PubMedPubMedCentralCrossRefGoogle Scholar
  103. 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 31:193–203PubMedCrossRefGoogle Scholar
  104. 104.
    Piekna-Przybylska D, Bambara RA, Balakrishnan L (2016) Acetylation regulates DNA repair mechanisms in human cells. Cell Cycle 15:1506–1517PubMedPubMedCentralCrossRefGoogle Scholar
  105. 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 45:8291–8301CrossRefGoogle Scholar
  106. 106.
    Carter RJ, Parsons JL (2016) Base excision repair, a pathway regulated by posttranslational modifications. Mol Cell Biol 36:1426–1437PubMedPubMedCentralCrossRefGoogle Scholar
  107. 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. PubMedPubMedCentralGoogle Scholar
  108. 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. PubMedPubMedCentralGoogle Scholar
  109. 109.
    Sadoul K, Boyault C, Pabion M, Khochbin S (2008) Regulation of protein turnover by acetyltransferases and deacetylases. Biochimie 90:306–312PubMedCrossRefGoogle Scholar
  110. 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 40:295–306PubMedCrossRefGoogle Scholar
  111. 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 41:1722–1733PubMedCrossRefGoogle Scholar
  112. 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 133:2444–2452PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Istituto di Genetica Molecolare del CNRPaviaItaly
  2. 2.IRBBarcelonaSpain

Personalised recommendations