Cell Cycle Regulates Nuclear Stability of AID and Determines the Cellular Response to AID
AID (Activation Induced Deaminase) deaminates cytosines in DNA to initiate immunoglobulin gene diversification and to reprogram the genome in early development. AID is potentially highly mutagenic, as it deaminates C to U within single-stranded regions. Here we show that AID abundance is regulated by cell cycle, and that high levels of nuclear AID are tolerated only in G1 phase. These results identify an unanticipated role for spatiotemporal regulation in balancing demands of AID-initiated mutagenesis and its potentially pathological outcomes.
Vyšlo v časopise:
Cell Cycle Regulates Nuclear Stability of AID and Determines the Cellular Response to AID. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005411
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1005411
Souhrn
AID (Activation Induced Deaminase) deaminates cytosines in DNA to initiate immunoglobulin gene diversification and to reprogram the genome in early development. AID is potentially highly mutagenic, as it deaminates C to U within single-stranded regions. Here we show that AID abundance is regulated by cell cycle, and that high levels of nuclear AID are tolerated only in G1 phase. These results identify an unanticipated role for spatiotemporal regulation in balancing demands of AID-initiated mutagenesis and its potentially pathological outcomes.
Zdroje
1. Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T (2000) Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102: 553–563. 11007474
2. Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O, Catalan N, Forveille M, Dufourcq-Labelouse R, Gennery A, Tezcan I, Ersoy F, Kayserili H, Ugazio AG, Brousse N, Muramatsu M, Notarangelo LD, Kinoshita K, Honjo T, Fischer A, Durandy A (2000) Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 102: 565–575. 11007475
3. Maizels N (2005) Immunoglobulin gene diversification. Annu Rev Genet 39: 23–46. 16285851
4. Di Noia JM, Neuberger MS (2007) Molecular mechanisms of antibody somatic hypermutation. Annu Rev Biochem 76: 1–22. 17328676
5. Lee-Theilen M, Chaudhuri J (2010) Walking the AID tightrope. Nat Immunol 11: 107–109. doi: 10.1038/ni0210-107 20084065
6. Gazumyan A, Bothmer A, Klein IA, Nussenzweig MC, McBride KM (2012) Activation-induced cytidine deaminase in antibody diversification and chromosome translocation. Adv Cancer Res 113: 167–190. doi: 10.1016/B978-0-12-394280-7.00005-1 22429855
7. Robbiani DF, Nussenzweig MC (2013) Chromosome translocation, B cell lymphoma, and activation-induced cytidine deaminase. Annu Rev Pathol 8: 79–103. doi: 10.1146/annurev-pathol-020712-164004 22974238
8. Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK (2004) Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming. J Biol Chem 279: 52353–52360. 15448152
9. Popp C, Dean W, Feng S, Cokus SJ, Andrews S, Pellegrini M, Jacobsen SE, Reik W (2010) Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature 463: 1101–1105. doi: 10.1038/nature08829 20098412
10. 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. doi: 10.1038/nature08752 20027182
11. Munoz DP, Lee EL, Takayama S, Coppe JP, Heo SJ, Boffelli D, Di Noia JM, Martin DI (2013) Activation-induced cytidine deaminase (AID) is necessary for the epithelial-mesenchymal transition in mammary epithelial cells. Proc Natl Acad Sci U S A 110: E2977–2986. doi: 10.1073/pnas.1301021110 23882083
12. Kumar R, DiMenna L, Schrode N, Liu TC, Franck P, Munoz-Descalzo S, Hadjantonakis AK, Zarrin AA, Chaudhuri J, Elemento O, Evans T (2013) AID stabilizes stem-cell phenotype by removing epigenetic memory of pluripotency genes. Nature 500: 89–92. doi: 10.1038/nature12299 23803762
13. Kuraoka M, Holl TM, Liao D, Womble M, Cain DW, Reynolds AE, Kelsoe G (2011) Activation-induced cytidine deaminase mediates central tolerance in B cells. Proc Natl Acad Sci U S A 108: 11560–11565. doi: 10.1073/pnas.1102571108 21700885
14. Meyers G, Ng YS, Bannock JM, Lavoie A, Walter JE, Notarangelo LD, Kilic SS, Aksu G, Debre M, Rieux-Laucat F, Conley ME, Cunningham-Rundles C, Durandy A, Meffre E (2011) Activation-induced cytidine deaminase (AID) is required for B-cell tolerance in humans. Proc Natl Acad Sci U S A 108: 11554–11559. doi: 10.1073/pnas.1102600108 21700883
15. Durandy A, Cantaert T, Kracker S, Meffre E (2013) Potential roles of activation-induced cytidine deaminase in promotion or prevention of autoimmunity in humans. Autoimmunity 46: 148–156. doi: 10.3109/08916934.2012.750299 23215867
16. Zan H, Casali P (2013) Regulation of Aicda expression and AID activity. Autoimmunity 46: 83–101. doi: 10.3109/08916934.2012.749244 23181381
17. Hasler J, Rada C, Neuberger MS (2012) The cytoplasmic AID complex. Semin Immunol 24: 273–280. doi: 10.1016/j.smim.2012.05.004 22698843
18. Orthwein A, Di Noia JM (2012) Activation induced deaminase: how much and where? Semin Immunol 24: 246–254. doi: 10.1016/j.smim.2012.05.001 22687198
19. Methot SP, Litzler LC, Trajtenberg F, Zahn A, Robert F, Pelletier J, Buschiazzo A, Magor BG, Di Noia JM (2015) Consecutive interactions with HSP90 and eEF1A underlie a functional maturation and storage pathway of AID in the cytoplasm. J Exp Med 212: 581–596. doi: 10.1084/jem.20141157 25824822
20. Aoufouchi S, Faili A, Zober C, D'Orlando O, Weller S, Weill JC, Reynaud CA (2008) Proteasomal degradation restricts the nuclear lifespan of AID. J Exp Med 205: 1357–1368. doi: 10.1084/jem.20070950 18474627
21. Orthwein A, Patenaude AM, Affar el B, Lamarre A, Young JC, Di Noia JM (2010) Regulation of activation-induced deaminase stability and antibody gene diversification by Hsp90. J Exp Med 207: 2751–2765. doi: 10.1084/jem.20101321 21041454
22. McBride KM, Barreto V, Ramiro AR, Stavropoulos P, Nussenzweig MC (2004) Somatic hypermutation is limited by CRM1-dependent nuclear export of activation-induced deaminase. J Exp Med 199: 1235–1244. 15117971
23. Ito S, Nagaoka H, Shinkura R, Begum N, Muramatsu M, Nakata M, Honjo T (2004) Activation-induced cytidine deaminase shuttles between nucleus and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1. Proc Natl Acad Sci U S A 101: 1975–1980. 14769937
24. Brar SS, Watson M, Diaz M (2004) Activation-induced cytosine deaminase (AID) is actively exported out of the nucleus but retained by the induction of DNA breaks. J Biol Chem 279: 26395–26401. 15087440
25. Wang M, Rada C, Neuberger MS (2010) Altering the spectrum of immunoglobulin V gene somatic hypermutation by modifying the active site of AID. J Exp Med 207: 141–153. doi: 10.1084/jem.20092238 20048284
26. Geisberger R, Rada C, Neuberger MS (2009) The stability of AID and its function in class-switching are critically sensitive to the identity of its nuclear-export sequence. Proc Natl Acad Sci U S A 106: 6736–6741. doi: 10.1073/pnas.0810808106 19351893
27. Zahn A, Eranki AK, Patenaude AM, Methot SP, Fifield H, Cortizas EM, Foster P, Imai K, Durandy A, Larijani M, Verdun RE, Di Noia JM (2014) Activation induced deaminase C-terminal domain links DNA breaks to end protection and repair during class switch recombination. Proc Natl Acad Sci U S A 111: E988–997. doi: 10.1073/pnas.1320486111 24591601
28. Ordinario EC, Yabuki M, Larson RP, Maizels N (2009) Temporal regulation of Ig gene diversification revealed by single-cell imaging. J Immunol 183: 4545–4553. doi: 10.4049/jimmunol.0900673 19748985
29. Yabuki M, Ordinario EC, Cummings WJ, Fujii MM, Maizels N (2009) E2A acts in cis in G1 phase of cell cycle to promote Ig gene diversification. J Immunol 182: 408–415. 19109172
30. Sharbeen G, Yee CW, Smith AL, Jolly CJ (2012) Ectopic restriction of DNA repair reveals that UNG2 excises AID-induced uracils predominantly or exclusively during G1 phase. J Exp Med 209: 965–974. doi: 10.1084/jem.20112379 22529268
31. Yamane A, Robbiani DF, Resch W, Bothmer A, Nakahashi H, Oliveira T, Rommel PC, Brown EJ, Nussenzweig A, Nussenzweig MC, Casellas R (2013) RPA accumulation during class switch recombination represents 5'-3' DNA-end resection during the S-G2/M phase of the cell cycle. Cell Rep 3: 138–147. doi: 10.1016/j.celrep.2012.12.006 23291097
32. Sakaue-Sawano A, Kurokawa H, Morimura T, Hanyu A, Hama H, Osawa H, Kashiwagi S, Fukami K, Miyata T, Miyoshi H, Imamura T, Ogawa M, Masai H, Miyawaki A (2008) Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell 132: 487–498. doi: 10.1016/j.cell.2007.12.033 18267078
33. Li MM, Emerman M (2011) Polymorphism in human APOBEC3H affects a phenotype dominant for subcellular localization and antiviral activity. J Virol 85: 8197–8207. doi: 10.1128/JVI.00624-11 21653666
34. Gazumyan A, Timachova K, Yuen G, Siden E, Di Virgilio M, Woo EM, Chait BT, Reina San-Martin B, Nussenzweig MC, McBride KM (2011) Amino-terminal phosphorylation of activation-induced cytidine deaminase suppresses c-myc/IgH translocation. Mol Cell Biol 31: 442–449. doi: 10.1128/MCB.00349-10 21135131
35. Ciccone M, Calin GA, Perrotti D (2015) From the Biology of PP2A to the PADs for Therapy of Hematologic Malignancies. Front Oncol 5: 21. doi: 10.3389/fonc.2015.00021 25763353
36. Basu U, Chaudhuri J, Alpert C, Dutt S, Ranganath S, Li G, Schrum JP, Manis JP, Alt FW (2005) The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation. Nature 438: 508–511. 16251902
37. Pasqualucci L, Kitaura Y, Gu H, Dalla-Favera R (2006) PKA-mediated phosphorylation regulates the function of activation-induced deaminase (AID) in B cells. Proc Natl Acad Sci U S A 103: 395–400. 16387847
38. McBride KM, Gazumyan A, Woo EM, Schwickert TA, Chait BT, Nussenzweig MC (2008) Regulation of class switch recombination and somatic mutation by AID phosphorylation. J Exp Med 205: 2585–2594. doi: 10.1084/jem.20081319 18838546
39. Basu U, Franklin A, Alt FW (2009) Post-translational regulation of activation-induced cytidine deaminase. Philos Trans R Soc Lond B Biol Sci 364: 667–673. doi: 10.1098/rstb.2008.0194 19010772
40. Cheng HL, Vuong BQ, Basu U, Franklin A, Schwer B, Astarita J, Phan RT, Datta A, Manis J, Alt FW, Chaudhuri J (2009) Integrity of the AID serine-38 phosphorylation site is critical for class switch recombination and somatic hypermutation in mice. Proc Natl Acad Sci U S A 106: 2717–2722. doi: 10.1073/pnas.0812304106 19196992
41. Polo SE, Jackson SP (2011) Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev 25: 409–433. doi: 10.1101/gad.2021311 21363960
42. Conticello SG, Langlois MA, Yang Z, Neuberger MS (2007) DNA deamination in immunity: AID in the context of its APOBEC relatives. Adv Immunol 94: 37–73. 17560271
43. Sideraki V, Wilson DK, Kurz LC, Quiocho FA, Rudolph FB (1996) Site-directed mutagenesis of histidine 238 in mouse adenosine deaminase: substitution of histidine 238 does not impede hydroxylate formation. Biochemistry 35: 15019–15028. 8942668
44. Sale JE, Calandrini DM, Takata M, Takeda S, Neuberger MS (2001) Ablation of XRCC2/3 transforms immunoglobulin V gene conversion into somatic hypermutation. Nature 412: 921–926. 11528482
45. Rada C, Jarvis JM, Milstein C (2002) AID-GFP chimeric protein increases hypermutation of Ig genes with no evidence of nuclear localization. Proc Natl Acad Sci U S A 99: 7003–7008. 12011459
46. Yabuki M, Fujii MM, Maizels N (2005) The MRE11-RAD50-NBS1 complex accelerates somatic hypermutation and gene conversion of immunoglobulin variable regions. Nat Immunol 6: 730–736. 15937485
47. Uchimura Y, Barton LF, Rada C, Neuberger MS (2011) REG-gamma associates with and modulates the abundance of nuclear activation-induced deaminase. J Exp Med 208: 2385–2391. doi: 10.1084/jem.20110856 22042974
48. Mehta A, Haber JE (2014) Sources of DNA double-strand breaks and models of recombinational DNA repair. Cold Spring Harb Perspect Biol 6: a016428. doi: 10.1101/cshperspect.a016428 25104768
49. Jansen JG, Langerak P, Tsaalbi-Shtylik A, van den Berk P, Jacobs H, de Wind N (2006) Strand-biased defect in C/G transversions in hypermutating immunoglobulin genes in Rev1-deficient mice. J Exp Med 203: 319–323. 16476771
50. Kano C, Hanaoka F, Wang JY (2012) Analysis of mice deficient in both REV1 catalytic activity and POLH reveals an unexpected role for POLH in the generation of C to G and G to C transversions during Ig gene hypermutation. Int Immunol 24: 169–174. doi: 10.1093/intimm/dxr109 22223762
51. Masuda K, Ouchida R, Hikida M, Kurosaki T, Yokoi M, Masutani C, Seki M, Wood RD, Hanaoka F, OW J (2007) DNA polymerases eta and theta function in the same genetic pathway to generate mutations at A/T during somatic hypermutation of Ig genes. J Biol Chem 282: 17387–17394. 17449470
52. Diamant N, Hendel A, Vered I, Carell T, Reissner T, de Wind N, Geacinov N, Livneh Z (2012) DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity. Nucleic Acids Res 40: 170–180. doi: 10.1093/nar/gkr596 21908406
53. Vuong BQ, Herrick-Reynolds K, Vaidyanathan B, Pucella JN, Ucher AJ, Donghia NM, Gu X, Nicolas L, Nowak U, Rahman N, Strout MP, Mills KD, Stavnezer J, Chaudhuri J (2013) A DNA break- and phosphorylation-dependent positive feedback loop promotes immunoglobulin class-switch recombination. Nat Immunol 14: 1183–1189. doi: 10.1038/ni.2732 24097111
54. Lambert LJ, Walker S, Feltham J, Lee HJ, Reik W, Houseley J (2013) Etoposide induces nuclear re-localisation of AID. PLoS One 8: e82110. doi: 10.1371/journal.pone.0082110 24324754
55. Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40: 179–204. doi: 10.1016/j.molcel.2010.09.019 20965415
56. Reina-San-Martin B, Difilippantonio S, Hanitsch L, Masilamani RF, Nussenzweig A, Nussenzweig MC (2003) H2AX is required for recombination between immunoglobulin switch regions but not for intra-switch region recombination or somatic hypermutation. J Exp Med 197: 1767–1778. 12810694
57. Sale JE, Neuberger MS (1998) TdT-accessible breaks are scattered over the immunoglobulin V domain in a constitutively hypermutating B cell line. Immunity 9: 859–869. 9881976
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2015 Číslo 9
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
Najčítanejšie v tomto čísle
- Arabidopsis AtPLC2 Is a Primary Phosphoinositide-Specific Phospholipase C in Phosphoinositide Metabolism and the Endoplasmic Reticulum Stress Response
- Bridges Meristem and Organ Primordia Boundaries through , , and during Flower Development in
- KLK5 Inactivation Reverses Cutaneous Hallmarks of Netherton Syndrome
- The Chromatin Protein DUET/MMD1 Controls Expression of the Meiotic Gene during Male Meiosis in