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PMID: 16537383 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The DNA repair genes XPB and XPD defend cells from retroviral infection.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 12 ·2006-03-21 ·Pages 4622-7

Yoder K, Sarasin A, Kraemer K, McIlhatton M, Bushman F, Fishel R

Abstract

Reverse transcription of retroviral RNA genomes produce a double-stranded linear cDNA molecule. A host degradation system prevents a majority of the cDNA molecules from completing the obligatory genomic integration necessary for pathogenesis. We demonstrate that the human TFIIH complex proteins XPB (ERCC3) and XPD (ERCC2) play a principal role in the degradation of retroviral cDNA. DNA repair-deficient XPB and XPD mutant cell lines exhibited an increase in transduction efficiency by both HIV- and Moloney murine leukemia virus-based retroviral vectors. Replicating Moloney murine leukemia virus viral production was greater in XPB or XPD mutant cells but not XPA mutant cells. Quantitative PCR showed an increase in total cDNA molecules, integrated provirus, and 2LTR circles in XPB and XPD mutant cells. In the presence of a reverse transcription inhibitor, the HIV cDNA appeared more stable in mutant XPB or XPD cells. These studies implicate the nuclear DNA repair proteins XPB and XPD in a cellular defense against retroviral infection.

MeSH Terms
Animals Cell Line DNA Helicases/genetics,physiology DNA Repair/genetics DNA, Complementary/metabolism DNA, Viral/metabolism DNA-Binding Proteins/genetics,physiology HIV/genetics,physiology Humans Kinetics Mice Moloney murine leukemia virus/genetics,physiology Transcription, Genetic Virus Replication Xeroderma Pigmentosum Group D Protein/genetics,physiology
Chemicals
DNA, Complementary DNA, Viral DNA-Binding Proteins XPBC-ERCC-3 protein DNA Helicases Xeroderma Pigmentosum Group D Protein
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Yoder Kristine
Department of Molecular Virology, and Ohio State University Comprehensive Cancer Center, Ohio State University College of Medicine, Columbus, OH 43210, USA.
Sarasin Alain
Kraemer Kenneth
McIlhatton Michael
Bushman Frederic
Fishel Richard
References (46)
46 references, click to expand
  1. Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy.
    J Virol. 2001 Jun;75(11):4999-5008 PMID: 11333879
  2. Purification of a Tat-associated kinase reveals a TFIIH complex that modulates HIV-1 transcription.
    EMBO J. 1997 May 15;16(10):2836-50 PMID: 9184228
  3. Posttranslational inhibition of Ty1 retrotransposition by nucleotide excision repair/transcription factor TFIIH subunits Ssl2p and Rad3p.
    Genetics. 1998 Apr;148(4):1743-61 PMID: 9560391
  4. The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys.
    Nature. 2004 Feb 26;427(6977):848-53 PMID: 14985764
  5. Basal transcription defect discriminates between xeroderma pigmentosum and trichothiodystrophy in XPD patients.
    Mol Cell. 2003 Jun;11(6):1635-46 PMID: 12820975
  6. Novel interaction of the Hsp90 chaperone machine with Ssl2, an essential DNA helicase in Saccharomyces cerevisiae.
    Curr Genet. 2005 Jun;47(6):368-80 PMID: 15871019
  7. ERCC2/XPD gene polymorphisms and cancer risk.
    Mutagenesis. 2002 Nov;17(6):463-9 PMID: 12435843
  8. Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene.
    Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8658-63 PMID: 9238033
  9. A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy.
    Hum Mutat. 1999;14(1):9-22 PMID: 10447254
  10. Methods for studying pro- and antiapoptotic genes in nonimmortal cells.
    Methods Cell Biol. 2001;66:197-227 PMID: 11396004
  11. Suppression of retroviral infection by the RAD52 DNA repair protein.
    EMBO J. 2004 Aug 18;23(16):3421-9 PMID: 15297876
  12. Roles of host cell factors in circularization of retroviral dna.
    Virology. 2003 Sep 15;314(1):460-7 PMID: 14517098
  13. Generation of helper-free amphotropic retroviruses that transduce a dominant-acting, methotrexate-resistant dihydrofolate reductase gene.
    Mol Cell Biol. 1985 Mar;5(3):431-7 PMID: 2985952
  14. A quantitative assay for HIV DNA integration in vivo.
    Nat Med. 2001 May;7(5):631-4 PMID: 11329067
  15. The relative expression of mutated XPB genes results in xeroderma pigmentosum/Cockayne's syndrome or trichothiodystrophy cellular phenotypes.
    Hum Mol Genet. 1999 Jun;8(6):1125-33 PMID: 10332046
  16. Ubiquitin ligase activity of TFIIH and the transcriptional response to DNA damage.
    Mol Cell. 2005 Apr 15;18(2):237-43 PMID: 15837426
  17. Nucleotide Excision Repair, Genome Stability, and Human Disease: New Insight from Model Systems.
    J Biomed Biotechnol. 2002;2(2):55-60 PMID: 12488584
  18. The human DNA repair gene, ERCC2 (XPD), corrects ultraviolet hypersensitivity and ultraviolet hypermutability of a shuttle vector replicated in xeroderma pigmentosum group D cells.
    Cancer Res. 1994 Jul 15;54(14):3837-44 PMID: 8033104
  19. DNA deamination mediates innate immunity to retroviral infection.
    Cell. 2003 Jun 13;113(6):803-9 PMID: 12809610
  20. Molecular mechanism of nucleotide excision repair.
    Genes Dev. 1999 Apr 1;13(7):768-85 PMID: 10197977
  21. Human immunodeficiency virus type 1 nucleocapsid zn(2+) fingers are required for efficient reverse transcription, initial integration processes, and protection of newly synthesized viral DNA.
    J Virol. 2003 Jan;77(2):1469-80 PMID: 12502862
  22. Evidence that stable retroviral transduction and cell survival following DNA integration depend on components of the nonhomologous end joining repair pathway.
    J Virol. 2004 Aug;78(16):8573-81 PMID: 15280466
  23. Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts.
    Nature. 2003 Jul 3;424(6944):99-103 PMID: 12808466
  24. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector.
    Science. 1996 Apr 12;272(5259):263-7 PMID: 8602510
  25. A role for DNA-PK in retroviral DNA integration.
    Science. 1999 Apr 23;284(5414):644-7 PMID: 10213687
  26. Nucleotide excision repair/TFIIH helicases RAD3 and SSL2 inhibit short-sequence recombination and Ty1 retrotransposition by similar mechanisms.
    Mol Cell Biol. 2000 Apr;20(7):2436-45 PMID: 10713167
  27. Stable SV40-transformation and characterisation of some DNA repair properties of fibroblasts from a trichothiodystrophy patient.
    Biochimie. 1995;77(11):906-12 PMID: 8824772
  28. Analysis of early human immunodeficiency virus type 1 DNA synthesis by use of a new sensitive assay for quantifying integrated provirus.
    J Virol. 2003 Sep;77(18):10119-24 PMID: 12941923
  29. Novel mutations in the RAD3 and SSL1 genes perturb genome stability by stimulating recombination between short repeats in Saccharomyces cerevisiae.
    Genetics. 1998 Nov;150(3):963-76 PMID: 9799251
  30. TFIIH inhibits CDK9 phosphorylation during human immunodeficiency virus type 1 transcription.
    J Biol Chem. 2001 Nov 30;276(48):44633-40 PMID: 11572868
  31. A colorimetric reverse transcriptase assay optimized for Moloney murine leukemia virus, and its use for characterization of reverse transcriptases of unknown identity.
    J Virol Methods. 1998 Nov;75(1):9-20 PMID: 9820570
  32. The 14th Datta Lecture. TFIIH: from transcription to clinic.
    FEBS Lett. 2001 Jun 8;498(2-3):124-8 PMID: 11412842
  33. The human and African green monkey TRIM5alpha genes encode Ref1 and Lv1 retroviral restriction factor activities.
    Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10780-5 PMID: 15249687
  34. The xeroderma pigmentosum group D (XPD) gene: one gene, two functions, three diseases.
    Genes Dev. 2001 Jan 1;15(1):15-23 PMID: 11156600
  35. Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection.
    EMBO J. 2001 Jun 15;20(12):3272-81 PMID: 11406603
  36. Class II integrase mutants with changes in putative nuclear localization signals are primarily blocked at a postnuclear entry step of human immunodeficiency virus type 1 replication.
    J Virol. 2004 Dec;78(23):12735-46 PMID: 15542626
  37. Expression of a transfected DNA repair gene (XPA) in xeroderma pigmentosum group A cells restores normal DNA repair and mutagenesis of UV-treated plasmids.
    Carcinogenesis. 1995 Jul;16(7):1557-63 PMID: 7614689
  38. Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5alpha.
    Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10774-9 PMID: 15249685
  39. DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy.
    Biochimie. 2003 Nov;85(11):1101-11 PMID: 14726016
  40. Recovery of normal DNA repair and mutagenesis in trichothiodystrophy cells after transduction of the XPD human gene.
    Cancer Res. 1996 Dec 1;56(23):5450-6 PMID: 8968100
  41. Human immunodeficiency virus cDNA metabolism: notable stability of two-long terminal repeat circles.
    J Virol. 2002 Apr;76(8):3739-47 PMID: 11907213
  42. DNA helicases, genomic instability, and human genetic disease.
    Annu Rev Genomics Hum Genet. 2000;1:409-59 PMID: 11701636
  43. Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences.
    Nat Genet. 2000 Jun;25(2):217-22 PMID: 10835641
  44. Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro.
    J Virol. 1992 Nov;66(11):6361-9 PMID: 1404595
  45. Female embryonic lethality in mice nullizygous for both Msh2 and p53.
    Nat Genet. 1997 Sep;17(1):114-8 PMID: 9288110
  46. DNA-Dependent protein kinase is not required for efficient lentivirus integration.
    J Virol. 2000 Dec;74(23):11278-85 PMID: 11070027
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0509828103
Published
2006-03-21
Epub
2006-00-13
Pages
4622-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1450221
Subset
IM
Grants
NCI NIH HHS · R01 CA056542 · United States
NIDDK NIH HHS · T32 DK007705 · United States
NCI NIH HHS · CA 56542 · United States
NIDDK NIH HHS · T32 DK 07705 · United States
External Links
PubMed source DOI: 10.1073/pnas.0509828103 PMC Full Text View journal details
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