Journal of Cell Science, Vol 110, Issue 10 1159-1168, Copyright © 1997 by Company of Biologists

JOURNAL ARTICLES

Translocation of a UV-damaged DNA binding protein into a tight association with chromatin after treatment of mammalian cells with UV light

VR Otrin, M McLenigan, M Takao, AS Levine and M Protic
Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

A UV-damaged DNA binding protein (UV-DDB) is the major source of UV-damaged DNA binding activity in mammalian cell extracts. This activity is defective in at least some xeroderma pigmentosum group E (XP-E) patients; microinjection of the UV-DDB protein into their fibroblasts corrects nucleotide excision repair (NER). In an in vitro reconstituted NER system, small amounts of UV-DDB stimulate repair synthesis a few fold. After exposure to UV, mammalian cells show an early dose-dependent inhibition of the extractable UV-DDB activity; this inhibition may reflect a tight association of the binding protein with UV-damaged genomic DNA. To investigate the dynamics and location of UV-DDB with respect to damaged chromatin in vivo, we utilized nuclear fractionation and specific antibodies and detected translocation of the p127 component of UV-DDB from a loose to a tight association with chromatinized DNA immediately after UV treatment. A similar redistribution was found for other NER proteins, i.e. XPA, RP-A and PCNA, suggesting their tighter association with genomic DNA after UV. These studies revealed a specific protein-protein interaction between UV-DDB/p127 and RP-A that appears to enhance binding of both proteins to UV-damaged DNA in vitro, providing evidence for the involvement of UV-DDB in the damage-recognition step of NER. Moreover, the kinetics of the reappearance of extractable UV-DDB activity after UV treatment of human cells with differing repair capacities positively correlate with the cell's capacity to repair 6-4 pyrimidine dimers (6-4 PD) in the whole genome, a result consistent with an in vivo role for UV-DDB in recognizing this type of UV lesion.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Wakasugi, H. Kasashima, Y. Fukase, M. Imura, R. Imai, S. Yamada, J. E. Cleaver, and T. Matsunaga Physical and functional interaction between DDB and XPA in nucleotide excision repair Nucleic Acids Res., February 1, 2009; 37(2): 516 - 525. [Abstract] [Full Text] [PDF]

				J. Guerrero-Santoro, M. G. Kapetanaki, C. L. Hsieh, I. Gorbachinsky, A. S. Levine, and V. Rapic-Otrin The Cullin 4B-Based UV-Damaged DNA-Binding Protein Ligase Binds to UV-Damaged Chromatin and Ubiquitinates Histone H2A Cancer Res., July 1, 2008; 68(13): 5014 - 5022. [Abstract] [Full Text] [PDF]

				M. S. Luijsterburg, J. Goedhart, J. Moser, H. Kool, B. Geverts, A. B. Houtsmuller, L. H. F. Mullenders, W. Vermeulen, and R. van Driel Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC J. Cell Sci., August 1, 2007; 120(15): 2706 - 2716. [Abstract] [Full Text] [PDF]

				M. G. Kapetanaki, J. Guerrero-Santoro, D. C. Bisi, C. L. Hsieh, V. Rapic-Otrin, and A. S. Levine The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites PNAS, February 21, 2006; 103(8): 2588 - 2593. [Abstract] [Full Text] [PDF]

				M. Reynolds, E. Peterson, G. Quievryn, and A. Zhitkovich Human Nucleotide Excision Repair Efficiently Removes Chromium-DNA Phosphate Adducts and Protects Cells against Chromate Toxicity J. Biol. Chem., July 16, 2004; 279(29): 30419 - 30424. [Abstract] [Full Text] [PDF]

				Q.-E. Wang, Q. Zhu, G. Wani, J. Chen, and A. A. Wani UV radiation-induced XPC translocation within chromatin is mediated by damaged-DNA binding protein, DDB2 Carcinogenesis, June 1, 2004; 25(6): 1033 - 1043. [Abstract] [Full Text] [PDF]

				S. Das, S. V. Ward, D. Markle, and C. E. Samuel DNA Damage-binding Proteins and Heterogeneous Nuclear Ribonucleoprotein A1 Function as Constitutive KCS Element Components of the Interferon-inducible RNA-dependent Protein Kinase Promoter J. Biol. Chem., February 20, 2004; 279(8): 7313 - 7321. [Abstract] [Full Text] [PDF]

				C. Obuse, H. Yang, N. Nozaki, S. Goto, T. Okazaki, and K. Yoda Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase Genes Cells, February 1, 2004; 9(2): 105 - 120. [Abstract] [Full Text] [PDF]

				V. Rapic-Otrin, V. Navazza, T. Nardo, E. Botta, M. McLenigan, D. C. Bisi, A. S. Levine, and M. Stefanini True XP group E patients have a defective UV-damaged DNA binding protein complex and mutations in DDB2 which reveal the functional domains of its p48 product Hum. Mol. Genet., July 1, 2003; 12(13): 1507 - 1522. [Abstract] [Full Text] [PDF]

				O. Leupin, S. Bontron, and M. Strubin Hepatitis B Virus X Protein and Simian Virus 5 V Protein Exhibit Similar UV-DDB1 Binding Properties To Mediate Distinct Activities J. Virol., June 1, 2003; 77(11): 6274 - 6283. [Abstract] [Full Text] [PDF]

				S. Bontron, N. Lin-Marq, and M. Strubin Hepatitis B Virus X Protein Associated with UV-DDB1 Induces Cell Death in the Nucleus and Is Functionally Antagonized by UV-DDB2 J. Biol. Chem., October 4, 2002; 277(41): 38847 - 38854. [Abstract] [Full Text] [PDF]

				V. Rapic-Otrin, M. P. McLenigan, D. C. Bisi, M. Gonzalez, and A. S. Levine Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation Nucleic Acids Res., June 1, 2002; 30(11): 2588 - 2598. [Abstract] [Full Text] [PDF]

				S. Kamiuchi, M. Saijo, E. Citterio, M. de Jager, J. H. J. Hoeijmakers, and K. Tanaka Translocation of Cockayne syndrome group A protein to the nuclear matrix: Possible relevance to transcription-coupled DNA repair PNAS, January 8, 2002; 99(1): 201 - 206. [Abstract] [Full Text] [PDF]

				M. C. Hollander, O. Kovalsky, J. M. Salvador, K. E. Kim, A. D. Patterson, D. C. Haines, and A. J. Fornace Jr. Dimethylbenzanthracene Carcinogenesis in Gadd45a-null Mice Is Associated with Decreased DNA Repair and Increased Mutation Frequency Cancer Res., March 1, 2001; 61(6): 2487 - 2491. [Abstract] [Full Text]

				R.D. WOOD, S.J. ARAUJO, R.R. ARIZA, D.P. BATTY, M. BIGGERSTAFF, E. EVANS, P.-H. GAILLARD, D. GUNZ, B. KOBERLE, I. KURAOKA, et al. DNA Damage Recognition and Nucleotide Excision Repair in Mammalian Cells Cold Spring Harb Symp Quant Biol, January 1, 2000; 65(0): 173 - 182. [Abstract] [PDF]

				T. Lindahl and R. D. Wood Quality Control by DNA Repair Science, December 3, 1999; 286(5446): 1897 - 1905. [Abstract] [Full Text]

				V. Otrin, I. Kuraoka, T. Nardo, M. McLenigan, A. P. M. Eker, M. Stefanini, A. S. Levine, and R. D. Wood Relationship of the Xeroderma Pigmentosum Group E DNA Repair Defect to the Chromatin and DNA Binding Proteins UV-DDB and Replication Protein A Mol. Cell. Biol., June 1, 1998; 18(6): 3182 - 3190. [Abstract] [Full Text]

				M. Wakasugi, A. Kawashima, H. Morioka, S. Linn, A. Sancar, T. Mori, O. Nikaido, and T. Matsunaga DDB Accumulates at DNA Damage Sites Immediately after UV Irradiation and Directly Stimulates Nucleotide Excision Repair J. Biol. Chem., January 11, 2002; 277(3): 1637 - 1640. [Abstract] [Full Text] [PDF]

				W. Liu, A. F. Nichols, J. A. Graham, R. Dualan, A. Abbas, and S. Linn Nuclear Transport of Human DDB Protein Induced by Ultraviolet Light J. Biol. Chem., July 7, 2000; 275(28): 21429 - 21434. [Abstract] [Full Text] [PDF]

				M. Wakasugi, M. Shimizu, H. Morioka, S. Linn, O. Nikaido, and T. Matsunaga Damaged DNA-binding Protein DDB Stimulates the Excision of Cyclobutane Pyrimidine Dimers in Vitro in Concert with XPA and Replication Protein A J. Biol. Chem., April 27, 2001; 276(18): 15434 - 15440. [Abstract] [Full Text] [PDF]