[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Skip to main content

Gadd45 in DNA Demethylation and DNA Repair

  • Chapter
  • First Online:
Gadd45 Stress Sensor Genes

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1360))

Abstract

Growth arrest and DNA damage 45 (Gadd45) family genes, Gadd45A, Gadd45B, and GADD45 G are implicated as stress sensors that are rapidly induced upon genotoxic/physiological stress. They are involved in regulation of various cellular functions such as DNA repair, senescence, and cell cycle control. Gadd45 family of genes serve as tumor suppressors in response to different stimuli and defects in Gadd45 pathway can give rise to oncogenesis. More recently, Gadd45 has been shown to promote gene activation by demethylation and this function is important for transcriptional regulation and differentiation during development. Gadd45 serves as an adaptor for DNA repair factors to promote removal of 5-methylcytosine from DNA at gene specific loci. Therefore, Gadd45 serves as a powerful link between DNA repair and epigenetic gene regulation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
GBP 19.95
Price includes VAT (United Kingdom)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
GBP 103.50
Price includes VAT (United Kingdom)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
GBP 129.99
Price includes VAT (United Kingdom)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
GBP 129.99
Price includes VAT (United Kingdom)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Abdollahi A, Lord KA, Hoffman-Liebermann B, Liebermann DA (1991) Sequence and expression of a cDNA encoding MyD118: a novel myeloid differentiation primary response gene induced by multiple cytokines. Oncogene 6:165–167

    CAS  PubMed  Google Scholar 

  • Agius F, Kapoor A, Zhu JK (2006) Role of the Arabidopsis DNA glycosylase/lyase ROS1 in active DNA demethylation. Proc Natl Acad Sci U S A 103:11796–11801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Azam N, Vairapandi M, Zhang W, Hoffman B, Liebermann DA (2001) Interaction of CR6 (GADD45 gamma) with proliferating cell nuclear antigen impedes negative growth control. J Biol Chem 276:2766–2774

    Article  CAS  PubMed  Google Scholar 

  • Barreto G, Schäfer A, Marhold J, Stach D, Swaminathan SK, Handa V, Doderlein G, Maltry N, Wu W, Lyko F et al (2007) Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature 445:671–675

    Article  CAS  PubMed  Google Scholar 

  • Beadling C, Johnson KW, Smith KA (1993) Isolation of interleukin 2-induced immediate-early genes. Proc Natl Acad Sci U S A 90:2719–2723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhutani N, Brady JJ, Damian M, Sacco A, Corbel SY, Blau HM (2010) Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 463:1042–1047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21

    Article  CAS  PubMed  Google Scholar 

  • Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE (2007) UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 317:1760–1764

    Article  CAS  PubMed  Google Scholar 

  • Bruniquel D, Schwartz RH (2003) Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nat Immunol 4:235–240

    Article  CAS  PubMed  Google Scholar 

  • Bulavin DV, Fornace AJ Jr (2004) p38 MAP kinases emerging role as tumor suppressor. Adv Cancer Res 92:95–118

    Article  CAS  PubMed  Google Scholar 

  • Bulavin DV, Kovalsky O, Hollander MC, Fornace AJ Jr (2003) Loss of oncogenic H-ras-induced cell cycle arrest and p38 mitogen-activated protein kinase activation by disruption of Gadd45a. Mol Cell Biol 23:3859–3871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caiafa P, Guastafierro T, Zampieri M (2009) Epigenetics: poly(ADP-ribosyl)ation of PARP-1 regulates genomic methylation patterns. FASEB J 23:672–678

    Article  CAS  PubMed  Google Scholar 

  • Carrier F, Georgel PT, Pourquier P, Blake M, Kontny HU, Antinore MJ, Gariboldi M, Myers TG, Weinstein JN, Pommier Y et al (1999) Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin. Mol Cell Biol 19:1673–1685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang Q, Bhatia D, Zhang Y, Meighan T, Castranova V, Shi X, Chen F (2007) Incorporation of an internal ribosome entry site-dependent mechanism in arsenic-induced GADD45 alpha expression. Cancer Res 67:6146–6154

    Article  CAS  PubMed  Google Scholar 

  • Cortellino S, Xu J, Sannai M, Moore R, Caretti E, Cigliana A, Le Coz M, Devarajan K, Wessels A, Soprano D et al (2011) Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell 146:67–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cretu A, Sha X, Tront J, Hoffman B, Liebermann DA (2009) Stress sensor Gadd45 genes as therapeutic targets in cancer. Cancer Ther 7:268–276

    CAS  PubMed  PubMed Central  Google Scholar 

  • Deaton AM, Bird A (2011) CpG islands and the regulation of transcription. Genes Dev 25:1010–1022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fornace AJ Jr, Alamo I Jr, Hollander MC (1988) DNA damage-inducible transcripts in mammalian cells. Proc Natl Acad Sci U S A 85:8800–8804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fornace AJ Jr, Nebert DW, Hollander MC, Luethy JD, Papathanasiou M, Fargnoli J, Holbrook NJ (1989) Mol Cell Biol 9(10):4196–4203

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fornace AJ Jr, Jackman J, Hollander MC, Hoffman-Liebermann B, Liebermann DA (1992) Genotoxic-stress-response genes and growth-arrest genes. gadd, MyD, and other genes induced by treatments eliciting growth arrest. Ann N Y Acad Sci 663:139–153

    Article  CAS  PubMed  Google Scholar 

  • Gao M, Guo N, Huang C, Song L (2009) Diverse roles of GADD45alpha in stress signaling. Curr Protein Pept Sci 10:388–394

    Article  CAS  PubMed  Google Scholar 

  • Gavin DP, Sharma RP, Chase KA, Matrisciano F, Dong E, Guidotti A (2012) Growth arrest and DNA-damage-inducible, beta (GADD45b)-mediated DNA demethylation in major psychosis. Neuropsychopharmacology 37:531–542

    Article  CAS  PubMed  Google Scholar 

  • Gjerset RA, Martin DW Jr (1982) Presence of a DNA demethylating activity in the nucleus of murine erythroleukemic cells. J Biol Chem 257:8581–8583

    Article  CAS  PubMed  Google Scholar 

  • Grin I, Ischenko AA (2016) An interplay of the base excision repair and mismatch repair pathways in active DNA demethylation. Nucleic Acids Res 44:3713–3727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo JU, Ma DK, Mo H, Ball MP, Jang MH, Bonaguidi MA, Balazer JA, Eaves HL, Xie B, Ford E et al (2011a) Neuronal activity modifies the DNA methylation landscape in the adult brain. Nat Neurosci 14:1345–1351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo JU, Su Y, Zhong C, Ming GL, Song H (2011b) Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145:423–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta M, Gupta SK, Balliet AG, Hollander MC, Fornace AJ, Hoffman B, Liebermann DA (2005) Hematopoietic cells from Gadd45a- and Gadd45b-deficient mice are sensitized to genotoxic-stress-induced apoptosis. Oncogene 24:7170–7179

    Article  CAS  PubMed  Google Scholar 

  • Hackett JA, Surani MA (2013) DNA methylation dynamics during the mammalian life cycle. Philos Trans R Soc Lond Ser B Biol Sci 368:20110328

    Article  CAS  Google Scholar 

  • Hackett JA, Sengupta R, Zylicz JJ, Murakami K, Lee C, Down TA, Surani MA (2013) Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine. Science 339:448–452

    Article  CAS  PubMed  Google Scholar 

  • Hajkova P, Jeffries SJ, Lee C, Miller N, Jackson SP, Surani MA (2010) Genome-wide reprogramming in the mouse germ line entails the base excision repair pathway. Science 329:78–82

    Article  CAS  PubMed  Google Scholar 

  • He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L et al (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333:1303–1307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hildesheim J, Bulavin DV, Anver MR, Alvord WG, Hollander MC, Vardanian L, Fornace AJ Jr (2002) Gadd45a protects against UV irradiation-induced skin tumors, and promotes apoptosis and stress signaling via MAPK and p53. Cancer Res 62:7305–7315

    CAS  PubMed  Google Scholar 

  • Hildesheim J, Belova GI, Tyner SD, Zhou X, Vardanian L, Fornace AJJ (2004) Gadd45a regulates 577 matrix metalloproteinases by suppressing DeltaNp63alpha and beta-catenin via p38 MAP 578 kinase and APC complex activation. Oncogene 23:1829–1837

    Article  CAS  PubMed  Google Scholar 

  • Hildesheim J, Salvador JM, Hollander MC, Fornace AJ Jr (2005) Casein kinase 2- and protein 580 kinase A-regulated adenomatous polyposis coli and {beta}-catenin cellular localization is 581 dependent on p38 MAPK. J Biol Chem 280:17221–17226

    Article  CAS  PubMed  Google Scholar 

  • Hollander MC, Fornace AJ Jr (2002) Genomic instability, centrosome amplification, cell cycle checkpoints and Gadd45a. Oncogene 21:6228–6233

    Article  CAS  PubMed  Google Scholar 

  • Hollander MC, Sheikh MS, Bulavin DV, Lundgren K, Augeri-Henmueller L, Shehee R, Molinaro TA, Kim KE, Tolosa E, Ashwell JD et al (1999) Genomic instability in Gadd45a-deficient mice. Nat Genet 23:176–184

    Article  CAS  PubMed  Google Scholar 

  • Hollander MC, Kovalsky O, Salvador JM, Kim KE, Patterson AD, Haines DC, Fornace AJ Jr (2001) Dimethylbenzanthracene carcinogenesis in Gadd45a-null mice is associated with decreased DNA repair and increased mutation frequency. Cancer Res 61:2487–2491

    CAS  PubMed  Google Scholar 

  • Hu XV, Rodrigues TM, Tao H, Baker RK, Miraglia L, Orth AP, Lyons GE, Schultz PG, Wu X (2010) Identification of RING finger protein 4 (RNF4) as a modulator of DNA demethylation through a functional genomics screen. Proc Natl Acad Sci U S A 107:15087–15092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imamura T, Yamamoto S, Ohgane J, Hattori N, Tanaka S, Shiota K (2004) Non-coding RNA directed DNA demethylation of Sphk1 CpG island. Biochem Biophys Res Commun 322:593–600

    Article  CAS  PubMed  Google Scholar 

  • Inoue A, Zhang Y (2011) Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos. Science 334:194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iqbal K, Jin SG, Pfeifer GP, Szabo PE (2011) Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc Natl Acad Sci U S A 108:3642–3647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333:1300–1303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin C, Qin T, Barton MC, Jelinek J et al (2015) Minimal role of base excision repair in TET-induced global DNA demethylation in HEK293T cells. Epigenetics 10:1006–1013

    Article  PubMed  PubMed Central  Google Scholar 

  • Jinawath N, Vasoontara C, Yap KL, Thiaville MM, Nakayama K, Wang TL, Shih IM (2009) NAC-1, a potential stem cell pluripotency factor, contributed to paclitaxel resistance in ovarian cancer through inactivating Gadd45 pathway. Oncogene 29:1941–1948

    Article  CAS  Google Scholar 

  • Jost JP (1993) Nuclear extracts of chicken embryos promote an active demethylation of DNA by excision repair of 5-methyldeoxycytidine. Proc Natl Acad Sci U S A 90:4684–4688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung HJ, Kim EH, Mun JY, Park S, Smith ML, Han SS, Seo YR (2007) Base excision DNA repair defect in Gadd45a-deficient cells. Oncogene 26:7517–7525

    Article  CAS  PubMed  Google Scholar 

  • Kaufmann LT, Gierl MS, Niehrs C (2011) Gadd45a, Gadd45b and Gadd45g expression during mouse embryonic development. Gene Expr Patterns 11:465–470

    Article  CAS  PubMed  Google Scholar 

  • Kearsey JM, Coates PJ, Prescott AR, Warbrick E, Hall PA (1995) Gadd45 is a nuclear cell cycle regulated protein which interacts with p21Cip1. Oncogene 11:1675–1683

    CAS  PubMed  Google Scholar 

  • Lal A, Gorospe M (2006) Egad, more forms of gene regulation: the gadd45a story. Cell Cycle 5:1422–1425

    Article  CAS  PubMed  Google Scholar 

  • Le May N, Mota-Fernandes D, Velez-Cruz R, Iltis I, Biard D, Egly JM (2010) NER factors are recruited to active promoters and facilitate chromatin modification for transcription in the absence of exogenous genotoxic attack. Mol Cell 38:54–66

    Article  PubMed  CAS  Google Scholar 

  • Lee B, Morano A, Porcellini A, Muller MT (2011) GADD45alpha inhibition of DNMT1 dependent DNA methylation during homology directed DNA repair. Nucleic Acids Res 40(6):2481–2493

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li Y, Zhao M, Yin H, Gao F, Wu X, Luo Y, Zhao S, Zhang X, Su Y, Hu N et al. (2010) Overexpression of the growth arrest and DNA damage-induced 45alpha gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells. Arthritis Rheum 62: 1438–1447.

    Google Scholar 

  • Li Z, Gu TP, Weber AR, Shen JZ, Li BZ, Xie ZG, Yin R, Guo F, Liu X, Tang F, Wang H, Schär P, Xu GL (2015) Gadd45a promotes DNA demethylation through TDG. Nucleic Acids Res 43(8):3986–3997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Marshall PR, Leighton LJ, Zajaczkowski EL, Wang Z, Madugalle SU, Yin J, Bredy TW, Wei W (2019) The DNA Repair-Associated Protein Gadd45 gamma regulates the temporal coding of immediate early gene expression within the prelimbic prefrontal cortex and is required for the consolidation of associative fear memory. J Neurosci 39(6):970–983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM et al (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462:315–322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H (2009) Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323:1074–1077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Magimaidas A, Madireddi P, Maifrede S, Mukherjee K, Hoffman B, Liebermann DA (2016) Gadd45b deficiency promotes premature senescence and skin aging. Oncotarget 7(19):26935–26948

    Article  PubMed  PubMed Central  Google Scholar 

  • Maiti A, Drohat AC (2011) Thymine DNA Glycosylase Can Rapidly Excise 5-Formylcytosine and 5-Carboxylcytosine: potential implications for active demethylation of cpg sites. J Biol Chem 286:35334–35338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mayer W, Niveleau A, Walter J, Fundele R, Haaf T (2000) Demethylation of the zygotic parental genome. Nature 403:501–502

    Article  CAS  PubMed  Google Scholar 

  • Mikkelsen TS, Hanna J, Zhang X, Ku M, Wernig M, Schorderet P, Bernstein BE, Jaenisch R, Lander ES, Meissner A (2008) Dissecting direct reprogramming through integrative genomic analysis. Nature 454:49–55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53:857–869

    Article  CAS  PubMed  Google Scholar 

  • Muller U, Bauer C, Siegi M, Rottach A et al (2014) TET-mediated oxidation of methylcytosine causes TDG or NEIL glycosylase dependent gene reactivation. Nucleic Acids Res 42:8592–8604

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Niehrs C (2009) Active DNA demethylation and DNA repair. Differentiation 77:1–11

    Article  CAS  PubMed  Google Scholar 

  • Niehrs C, Schäfer A (2012) Active DNA demethylation by Gadd45 and DNA repair. Trends Cell Biol 22:220–227

    Article  CAS  PubMed  Google Scholar 

  • Oda M, Oxley D, Dean W, Reik W (2013) Regulation of lineage specific DNA hypomethylation in mouse trophectoderm. PLoS One 8(6):e68846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oswald J, Engemann S, Lane N, Mayer W, Olek A, Fundele R, Dean W, Reik W, Walter J (2000) Active demethylation of the paternal genome in the mouse zygote. Curr Biol 10:475–478

    Article  CAS  PubMed  Google Scholar 

  • Rai K, Huggins IJ, James SR, Karpf AR, Jones DA, Cairns BR (2008) DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell 135:1201–1212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santos-Rosa H, Schneider R, Bannister AJ, Sherriff J, Bernstein BE, Emre NC, Schreiber SL, Mellor J, Kouzarides T (2002) Active genes are tri-methylated at K4 of histone H3. Nature 419:407–411

    Article  CAS  PubMed  Google Scholar 

  • Schäfer A, Karaulanov E, Stapf U, Doderlein G, Niehrs C (2013) Ing1 functions in DNA demethylation by directing Gadd45a to H3K4me3. Genes Dev 27:261–273

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schmitz KM, Schmitt N, Hoffmann-Rohrer U, Schäfer A, Grummt I, Mayer C (2009) TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation. Mol Cell 33:344–353

    Article  CAS  PubMed  Google Scholar 

  • Schneider R, Bannister AJ, Myers FA, Thorne AW, Crane-Robinson C, Kouzarides T (2004) Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat Cell Biol 6:73–77

    Article  CAS  PubMed  Google Scholar 

  • Sen GL, Reuter JA, Webster DE, Zhu L, Khavari PA (2010) DNMT1 maintains progenitor function in self-renewing somatic tissue. Nature 463:563–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao S, Wang Y, Jin S, Song Y, Wang X, Fan W, Zhao Z, Fu M, Tong T, Dong L, Fan F, Xu N, Zhan Q (2006) Gadd45a interacts with aurora-A and inhibits its kinase activity. J Biol Chem 281:28943–28950

    Article  CAS  PubMed  Google Scholar 

  • Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O’Connor PM, Fornace AJ Jr (1994) Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science 266:1376–1380

    Article  CAS  PubMed  Google Scholar 

  • Smith ML, Kontny HU, Zhan Q, Sreenath A, O’Connor PM, Fornace AJ Jr (1996) Antisense GADD45 expression results in decreased DNA repair and sensitizes cells to u.v.-irradiation or cisplatin. Oncogene 13:2255–2263

    CAS  PubMed  Google Scholar 

  • Smith ML, Ford JM, Hollander MC, Bortnick RA, Amundson SA, Seo YR, Deng CX, Hanawalt PC, Fornace AJ Jr (2000) p53-mediated DNA repair responses to UV radiation: studies of mouse cells lacking p53, p21, and/or gadd45 genes. Mol Cell Biol 20:3705–3714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stadler MB, Murr R, Burger L, Ivanek R, Lienert F, Scholer A, van Nimwegen E, Wirbelauer C, Oakeley EJ, Gaidatzis D et al (2011) DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature 480:490–495

    Article  CAS  PubMed  Google Scholar 

  • Sytnikova YA, Kubarenko AV, Schäfer A, Weber AN, Niehrs C (2011) Gadd45a is an RNA binding protein and is localized in nuclear speckles. PLoS One 6:e14500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L et al (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takekawa M, Saito H (1998) A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK. Cell 95:521–530

    Article  CAS  PubMed  Google Scholar 

  • Tian J, Huang H, Hoffman B, Liebermann DA, Ledda-Columbano GM, Columbano A, Locker J (2011) Gadd45beta is an inducible coactivator of transcription that facilitates rapid liver growth in mice. J Clin Invest 121:4491–4502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tong T, Ji J, Jin S, Li X, Fan W, Song Y, Wang M, Liu Z, Wu M, Zhan Q (2005) Gadd45a expression induces Bim dissociation from the cytoskeleton and translocation to mitochondria. Mol Cell Biol 25:4488–4500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ulrey CL, Liu L, Andrews LG, Tollefsbol TO (2005) The impact of metabolism on DNA methylation. Hum Mol Genet 14 Spec No 1:R139–R147

    Google Scholar 

  • Vairapandi M, Balliet AG, Fornace AJ Jr, Hoffman B, Liebermann DA (1996) The differentiation primary response gene MyD118, related to GADD45, encodes for a nuclear protein which interacts with PCNA and p21WAF1/CIP1. Oncogene 12:2579–2594

    CAS  PubMed  Google Scholar 

  • Vairapandi M, Balliet AG, Hoffman B, Liebermann DA (2002) GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress. J Cell Physiol 192:327–338

    Article  CAS  PubMed  Google Scholar 

  • Wang XW, Wang RH, Li W, Xu X, Hollander C, Fornace A, Deng C (2004) Genetic interactions between Brca1 and Gadd45a in centrosome duplication, genetic stability and neural tube closure. J Biol Chem 279:29606–29614

    Article  CAS  PubMed  Google Scholar 

  • Weiss A, Keshet I, Razin A, Cedar H (1996) DNA demethylation in vitro: involvement of RNA. Cell 86:709–718

    Article  CAS  PubMed  Google Scholar 

  • Wossidlo M, Nakamura T, Lepikhov K, Marques CJ, Zakhartchenko V, Boiani M, Arand J, Nakano T, Reik W, Walter J (2011) 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat Commun 2:241

    Article  PubMed  CAS  Google Scholar 

  • Wu SC, Zhang Y (2010) Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol 11:607–620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xue JH, Xu GF, Gu TP, Chen GD et al (2016) Uracil-DNA glycosylase UNG promotes Tet-mediated DNA demethylation. J Biol Chem 291:731–738

    Article  CAS  PubMed  Google Scholar 

  • Yi YW, Kim D, Jung N, Hong SS, Lee HS, Bae I (2000) Gadd45 family proteins are coactivators of nuclear hormone receptors. Biochem Biophys Res Commun 272:193–198

    Article  CAS  PubMed  Google Scholar 

  • Zampieri M, Passananti C, Calabrese R, Perilli M, Corbi N, De Cave F, Guastafierro T, Bacalini MG, Reale A, Amicosante G, Calabrese L, Zlatanova J, Caiafa P (2009) Parp1 localizes within Dnmt1 promoter and protects its unmethylated state by its enzymatic activity. PLoS One 4:e4717

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zerbini LF, Wang Y, Czibere A, Correa RG, Cho JY, Ijiri K, Wei W, Joseph M, Gu X, Grall F, Goldring MB, Zhou JR, Libermann TA (2004) NF-kappa B-mediated repression of growth arrest- and DNA-damage-inducible proteins 45alpha and gamma is essential for cancer cell survival. Proc Natl Acad Sci U S A 101:13618–13623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhan Q, Lord KA, Alamo I Jr, Hollander MC, Carrier F, Ron D, Kohn KW, Hoffman B, Liebermann DA, Fornace AJ Jr (1994) The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth. Mol Cell Biol 14:2361–2371

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhan Q, Fan S, Smith ML, Bae I, Yu K, Alamo I Jr, O’Connor PM, Fornace AJ Jr (1996) Abrogation of p53 function affects gadd gene responses to DNA base-damaging agents and starvation. DNA Cell Biol 15:805–815

    Article  CAS  PubMed  Google Scholar 

  • Zhan Q, Antinore MJ, Wang XW, Carrier F, Smith ML, Harris CC, Fornace AJJ (1999) Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45. Oncogene 18:2892–2900

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Bae I, Krishnaraju K, Azam N, Fan W, Smith K, Hoffman B, Liebermann DA (1999) CR6: a third member in the MyD118 and Gadd45 gene family which functions in negative growth control. Oncogene 18:4899–4907

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Pomerantz JH, Sen G, Palermo AT, Blau HM (2007) Active tissue-specific DNA demethylation conferred by somatic cell nuclei in stable heterokaryons. Proc Natl Acad Sci U S A 104:4395–4400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang RP, Shao JZ, Xiang LX (2011) GADD45A protein plays an essential role in active DNA demethylation during terminal osteogenic differentiation of adipose-derived mesenchymal stem cells. J Biol Chem 286:41083–41094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng X, Pontes O, Zhu J, Miki D, Zhang F, Li WX, Iida K, Kapoor A, Pikaard CS, Zhu JK (2008) ROS3 is an RNA-binding protein required for DNA demethylation in Arabidopsis. Nature 455:1259–1262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gurushankar Chandramouly .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chandramouly, G. (2022). Gadd45 in DNA Demethylation and DNA Repair. In: Zaidi, M.R., Liebermann, D.A. (eds) Gadd45 Stress Sensor Genes. Advances in Experimental Medicine and Biology, vol 1360. Springer, Cham. https://doi.org/10.1007/978-3-030-94804-7_4

Download citation

Publish with us

Policies and ethics