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Cited by 42DNA Repair MechanismsNuclear Structure and FunctionEffects of Radiation Exposure

UV-dependent interaction between Cep164 and XPA mediates localization of Cep164 at sites of DNA damage and UV sensitivity

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Pan, Yen-Ru, Lee, Eva Y.-H. P.·2009·Cell Cycle
DOI 10.4161/cc.8.4.7844
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Abstract

DNA damage response plays a critical role in the maintenance of genomic stability. In response to UV damage, ataxia telangiectasia mutated and rad3 related kinase (ATR)-mediated checkpoint and nucleotide excision repair (NER) machinery are activated. A centrosomal protein, Cep164, has been identified as a chromatin binding mediator protein functioning in ATR-mediated checkpoint activation upon UV damage. However, it was not clear whether there is cross talk between Cep164 and NER machinery. We show that Cep164 knockdown compromises the cell survival upon UV damage. Cep164 localizes to cyclobutane pyrimidine dimmers (CPD), one of the major DNA lesions induced by UV irradiation. Binding of Cep164 to the region of exon 4 to intron 9 within p53 gene, known as a pyrimidine-rich region as well as a photoproduct formation region upon UV damage, increases 2.5-fold upon UV irradiation. Recruitment of Cep164 to CPD sites or photoproduct formation region requires a NER factor, Xeroderma pigmentosum group A (XPA). Furthermore, UV irradiation significantly enhances the interaction between Cep164 and XPA. Cep164 binds to amino acids 4-97 of XPA, a region required for UV resistance. Importantly, co-localization of Cep164 and CPD is aberrant in XPA-deficient fibroblasts complemented with XPA(Delta10-88) mutant. In addition, UV-induced CHK1 phosphorylation is impaired in these cells. These findings provide mechanistic insights for the recruitment of Cep164 mediator protein to DNA damage sites and reveal a critical juncture between checkpoint pathways and repair systems.

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  • Cep164 is recruited to CPD sites in a NER-dependent manner through UV-induced physical interaction with XPA.

    “analogously, Cep164, a checkpoint mediator protein in the ATR signaling pathway required for Chk1 phosphorylation after UV damage, was shown to be recruited to CPD sites in a NER-dependent manner, through UV-induced physical interaction with XPA [93].”

    From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [93]

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Research works printed but not linked: 64

  1. Friedberg EC. DNA damage and repair. Nature 2003; 421:436-40.
  2. Lindahl T. Instability and decay of the primary structure of DNA. Nature 1993; 362:709-15.
  3. Friedberg EC. Out of the shadows and into the light-the emergence of DNA-repair. Trends Biochem Sci 1995; 20:381.
  4. Sinha RP, Hader DP. UV-induced DNA damage and repair: a review. Photochem Photobiol Sci 2002; 1:225-36.
  5. Abraham RT. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 2001; 15:2177-96. Cep164 and nucleotide excision repair proteins in DNA damage response 37. Boyle J, Ueda T, Oh KS, Imoto K, Tamura D, Jagdeo J, et al. Persistence of repair proteins at unrepaired DNA damage distinguishes diseases with ERCC2 (XPD) mutations: Cancer- prone Xeroderma pigmentosum vs. non-cancer-prone Trichothiodystrophy. Hum Mutat 2008; 29:1194-208.
  6. Lisby M, Barlow JH, Burgess RC, Rothstein R. Choreography of the DNA damage response: Spatiotemporal relationships among checkpoint and repair proteins. Cell 2004; 118:699-713.
  7. Volker M, Mone MJ, Karmakar P, van Hoffen A, Schul W, Vermeulen W, et al. Sequential assembly of the nucleotide excision repair factors in vivo. Mol Cell 2001; 8:213-24.
  8. Levy DD, Saijo M, Tanaka K, Kraemer KH. Expression of a transfected DNA-repair gene (XPA) in xeroderma pigmentosum group A cells restores normal DNA-repair and mutagen- esis of UV-treated plasmids. Carcinogenesis 1995; 16:1557-63.
  9. Jiang GC, Sancar A. Recruitment of DNA damage checkpoint proteins to damage in tran- scribed and nontranscribed sequences. Mol Cell Biol 2006; 26:39-49.
  10. Tornaletti S, Rozek D, Pfeifer GP. The distribution of UV photoproducts along the human p53 gene and its relation to mutations in skin cancer. Oncogene 1993; 8:2051-7.
  11. Barlow JH, Lisby M, Rothstein R. Differential regulation of the cellular response to DNA double-strand breaks in G 1 . Mol Cell 2008; 30:73-85.
  12. de Laat WL, Jaspers NGJ, Hoeijmakers JHJ. Molecular mechanism of nucleotide excision repair. Genes Dev 1999; 13:768-85.
  13. Shuck SC, Short EA, Turchi JJ. Eukaryotic nucleotide excision repair: From understanding mechanisms to influencing biology. Cell Res 2008; 18:64-72.
  14. Jones CJ, Wood RD. Preferential binding of the Xeroderma-pigmentosum Group-A complementing protein to damaged DNA. Biochemistry 1993; 32:12096-104.
  15. Miyamoto I, Miura N, Niwa H, Miyazaki J, Tanaka K. Mutational analysis of the structure and function of the Xeroderma-pigmentosum Group-A complementing protein-Identifi- cation of essential domains for nuclear-localization and DNA excision repair. J Biol Chem 1992; 267:12182-7.
  16. Bree RT, Neary C, Samali A, Lowndes NF. The switch from survival responses to apoptosis after chromosomal breaks. DNA Repair 2004; 3:989-95.
  17. MacDougall CA, Byun TS, Van C, Yee MC, Cimprich KA. The structural determinants of checkpoint activation. Genes Dev2007; 21:898-903.
  18. Marini F, Nardo T, Giannattasio M, Minuzzo M, Stefanini M, Plevani P, et al. DNA nucle- otide excision repair-dependent signaling to checkpoint activation. Proc Natl Acad Sci USA 2006; 103:17325-30.
  19. Marti TM, Hefner E, Feeney L, Natale V, Cleaver JE. H2AX phosphorylation within the G(1) phase after UV irradiation depends on nucleotide excision repair and not DNA double-strand breaks. Proc Natl Acad Sci USA 2006; 103:9891-6.
  20. Matsumoto M, Yaginuma K, Igarashi A, Imura M, Hasegawa M, Iwabuchi K, et al. Perturbed gap-filling synthesis in nucleotide excision repair causes histone H2AX phospho- rylation in human quiescent cells. J Cell Sci 2007; 120:1104-12.
  21. O'Driscoll M, Ruiz-Perez VL, Woods CG, Jeggo PA, Goodship JA. A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat Genet 2003; 33:497-501.
  22. Coin F, Oksenych V, Mocquet V, Groh S, Blattner C, Egly JM. Nucleotide excision repair driven by the dissociation of CAK from TFIIH. Mol Cell 2008; 31:9-20.
  23. Brueckner F, Hennecke U, Carell T, Cramer P. CPD damage recognition by transcribing RNA polymerase II. Science 2007; 315:859-62.
  24. Wu X, Shell SM, Liu Y, Zou Y. ATR-dependent checkpoint modulates XPA nuclear import in response to UV irradiation. Oncogene 2007; 26:757-64.
  25. Ikegami T, Kuraoka I, Saijo M, Kodo N, Kyogoku Y, Morikawa K, et al. Solution structure of the DNA-and RPA-binding domain of the human repair factor XPA. Nat Struct Biol 1998; 5:701-6.
  26. Ikegami T, Kuraoka I, Saijo M, Kodo N, Kyogoku Y, Morikawa K, et al. Resonance assign- ments, solution structure and backbone dynamics of the DNA-and RPA-binding domain of human repair factor XPA. J Biochem 1999; 125:495-506.
  27. Morikawa K, Shirakawa M. Three-dimensional structural views of damaged-DNA recogni- tion: T4 endonuclease V, E. coli Vsr protein, and human nucleotide excision repair factor XPA. Mutat Res 2000; 460:257-75.
  28. Bartels CL, Lambert MW. Domains in the XPA protein important in its role as a processiv- ity factor. Biochem Biophys Res Commun 2007; 356:219-25.
  29. Saijo M, Kuraoka I, Masutani C, Hanaoka F, Tanaka K. Sequential binding of DNA repair proteins RPA and ERCC1 to XPA in vitro. Nucleic Acids Res 1996; 24:4719-24.
  30. Farr PM, Besag JE, Diffey BL. The time course of Uvb and Uvc erythema. J Invest Dermatol 1988; 91:454-7.
  31. de Boer J, Hoeijmakers JHJ. Nucleotide excision repair and human syndromes. Carcinogenesis 2000; 21:453-60.
  32. Kuo MH, Allis CD. In vivo cross-linking and immunoprecipitation for studying dynamic protein: DNA associations in chromatin environment. Methods 1999; 19:425-33.
  33. Onclercq-Delic R, Calsou P, Delteil C, Salles B, Papadopoulo D, Amor-Gueret M. Possible anti-recombinogenic role of Bloom's syndrome helicase in double-strand break processing. Nucleic Acids Res 2003; 31:6272-82.
  34. Mitchell JR, Hoeijmakers JHJ, Niedernhofer LJ. Divide and conquer: nucleotide excision repair battles cancer and ageing. Curr Opin Cell Biol 2003; 15:232-40.
  35. Cimprich KA, Shin TB, Keith CT, Schreiber SL. cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein. Proc Natl Acad Sci USA 1996; 93:2850-5.
  36. Goodship J, Gill H, Carter J, Jackson A, Splitt M, Wright M. Autozygosity mapping of a Seckel syndrome locus to chromosome 3q22.1-q24. Am J Hum Genet 2000; 67:498-503.
  37. Shiloh Y. ATM and related protein kinases: Safeguarding genome integrity. Nat Rev Cancer 2003; 3:155-68.
  38. Bao SD, Tibbetts RS, Brumbaugh KM, Fang YN, Richardson DA, Ali A, et al. ATR/ ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses. Nature 2001; 411:969-74.
  39. Post S, Weng YC, Cimprich K, Chen LB, Xu Y, Lee EYHP. Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle regulated and is required for G(1)/S checkpoint activation in response to DNA damage. Proc Natl Acad Sci USA 2001; 98:13102-7.
  40. Post SM, Tomkinson AE, Lee EYHP. The human checkpoint Rad protein Rad17 is chro- matin-associated throughout the cell cycle, localizes to DNA replication sites, and interacts with DNA polymerase epsilon. Nucleic Acids Res 2003; 31:5568-75.
  41. Stiff T, Walker SA, Cerosaletti K, Goodarzi AA, Petermann E, Concannon P, et al. ATR- dependent phosphorylation and activation of ATM in response to UV treatment or replica- tion fork stalling. EMBO J 2006; 25:5775-82.
  42. Zhao H, Piwnica-Worms H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol Cell Biol 2001; 21:4129-39.
  43. Leung-Pineda V, Ryan CE, Piwnica-Worms H. Phosphorylation of Chk1 by ATR is antago- nized by a Chk1-regulated protein phosphatase 2A circuit. Mol Cell Biol 2006; 26:7529-38.
  44. Unsal-Kacmaz K, Makhov AM, Griffith JD, Sancar A. Preferential binding of ATR protein to UV-damaged DNA. Proc Natl Acad Sci USA 2002; 99:6673-8.
  45. Jazayeri A, Falck J, Lukas C, Bartek J, Smith GCM, Lukas J, et al. ATM-and cell cycle- dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol 2006; 8:13-37.
  46. Myers JS, Cortez D. Rapid activation of ATR by ionizing radiation requires ATM and Mre11. J Biol Chem 2006; 281:9346-50.
  47. Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. Molecular mechanisms of mamma- lian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 2004; 73:39-85.
  48. Evans E, Moggs JG, Hwang JR, Egly JM, Wood RD. Mechanism of open complex and dual incision formation by human nucleotide excision repair factors. EMBO J 1997; 16:6559-73.
  49. Mu D, Hsu DS, Sancar A. Reaction mechanism of human DNA repair excision nuclease. J Biol Chem 1996; 271:8285-94.
  50. Mu D, Park CH, Matsunaga T, Hsu DS, Reardon JT, Sancar A. Reconstitution of human DNA-repair excision nuclease in a highly defined system. J Biol Chem 1995; 270:2415-8.
  51. Ford JM, Hanawalt PC. Role of DNA excision repair gene defects in the etiology of cancer. Curr Top Microbiol Immunol 1997; 221:47-70.
  52. Lehmann AR. DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syn- drome and trichothiodystrophy. Biochimie 2003; 85:1101-11.
  53. Rouse J, Jackson SP. Interfaces between the detection, signaling and repair of DNA damage. Science 2002; 297:547-51.
  54. Giannattasio M, Lazzaro F, Longhese MP, Plevani P, Muzi-Falconi M. Physical and functional interactions between nucleotide excision repair and DNA damage checkpoint. EMBO J 2004; 23:429-38.
  55. Giannattasio M, Lazzaro F, Siede W, Nunes E, Plevani P, Muzi-Falconi M. DNA decay and limited Rad53 activation after liquid holding of UV-treated nucleotide excision repair deficient S. cerevisiae cells. DNA Repair 2004; 3:1591-9.
  56. Neecke H, Lucchini G, Longhese MP. Cell cycle progression in the presence of irreparable DNA damage is controlled by a Mec1-and Rad53-dependent checkpoint in budding yeast. EMBO J 1999; 18:4485-97.
  57. Bomgarden D, Lupardus PJ, Soni DV, Yee MC, Ford JM, Cimprich KA. Opposing effects of the UV lesion repair protein XPA and UV bypass polymerase eta on ATR checkpoint signaling. EMBO J 2006; 25:2605-14.
  58. Wu XM, Shell SM, Yang ZG, Zou Y. Phosphorylation of nucleotide excision repair fac- tor xeroderma pigmentosum group a by ataxia telangiectasia mutated and Rad3-related- dependent checkpoint pathway promotes cell survival in response to UV irradiation. Cancer Res 2006; 66:2997-3005.
  59. Cortez D, Guntuku S, Qin J, Elledge SJ. ATR and ATRIP: Partners in checkpoint signaling. Science 2001; 294:1713-6.
  60. Zou L, Elledge SJ. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 2003; 300:1542-8.
  61. Dodson GE, Shi YL, Tibbetts RS. DNA replication defects, spontaneous DNA damage, and ATM-dependent checkpoint activation in replication protein A-deficient cells. J Biol Chem 2004; 279:34010-4.
  62. Andersen JS, Wilkinson CJ, Mayor T, Mortensen P, Nigg EA, Mann M. Proteomic character- ization of the human centrosome by protein correlation profiling. Nature 2003; 426:570-4.
  63. Graser S, Stierhof YD, Lavoie SB, Gassner OS, Lamla S, Le Clech M, et al. Cep164, a novel centriole appendage protein required for primary cilium formation. J Cell Biol 2007; 179:321-30.
  64. Sivasubramaniam S, Sun XM, Pan YR, Wang SH, Lee EYHP. Cep164 is a mediator protein required for the maintenance of genomic stability through modulation of MDC1, RPA and CHK1. Genes Dev 2008; 22:587-600.

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Authors
Pan, Y.-R., & Lee, E. Y.-H. P.
Affiliations
University of California, Irvine (US)
Corresponding author
Lee, Eva Y.-H. P.
Venue
Cell Cycle
Publisher
Informa UK Limited
Published
2009-02-15
Volume
8
Issue
4
Pages
655-664
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
DOI
10.4161/cc.8.4.7844
OpenAlex
W2026985179
Cited by
42
References
0
Citations by year
2026: 2 · 2025: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 4 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 5
FWCI
1.48
Type
journal article
Language
en
Open access
Locations
  • Cell Cycle (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Defense (W81XWH)
  • Breast Cancer Research Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords
CEP164, XPA, nucleotide excision repair, UV damage, DNA damage response, ATR checkpoint, cyclobutane pyrimidine dimers, photoproducts, Chk1 phosphorylation, centrosomal proteins, UV sensitivity
MeSH terms
Animals, Carrier Proteins, DNA, DNA Damage, DNA Repair, HeLa Cells, Humans, Microtubule Proteins, Pyrimidines, Recombinant Fusion Proteins, Ultraviolet Rays, Tumor Suppressor Protein p53, RNA, Small Interfering, Genomic Instability, Xeroderma Pigmentosum Group A Protein, Gene Knockdown Techniques

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