Home LiteratureArticle Details
PMID: 14577841 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome DNA helicase.

BMC cell biology ·Vol. 4 ·2003-10-27 ·Pages 15

Schawalder J, Paric E, Neff NF

Abstract

Bloom syndrome is one of the most cancer-predisposing disorders and is characterized by genomic instability and a high frequency of sister chromatid exchange. The disorder is caused by loss of function of a 3' to 5' RecQ DNA helicase, BLM. The exact role of BLM in maintaining genomic integrity is not known but the helicase has been found to associate with several DNA repair complexes and some DNA replication foci. Chromatin immunoprecipitation of BLM complexes recovered telomere and ribosomal DNA repeats. The N-terminus of BLM, required for NB localization, is the same as the telomere association domain of BLM. The C-terminus is required for ribosomal DNA localization. BLM localizes primarily to the non-transcribed spacer region of the ribosomal DNA repeat where replication forks initiate. Bloom syndrome cells expressing the deletion alleles lacking the ribosomal DNA and telomere association domains have altered cell cycle populations with increased S or G2/M cells relative to normal. These results identify telomere and ribosomal DNA repeated sequence elements as chromosomal targets for the BLM DNA helicase during the S/G2 phase of the cell cycle. BLM is localized in nuclear bodies when it associates with telomeric repeats in both telomerase positive and negative cells. The BLM DNA helicase participates in genomic stability at ribosomal DNA repeats and telomeres.

MeSH Terms
Adenosine Triphosphatases/analysis,chemistry,metabolism Alleles Binding Sites Bloom Syndrome/enzymology,etiology,genetics Cell Cycle Cell Line Cell Nucleolus/enzymology Cell Nucleus Structures/enzymology Chromosomes/enzymology,ultrastructure DNA Helicases/analysis,chemistry,metabolism DNA Repair DNA Replication DNA, Ribosomal/analysis,chemistry Genetic Variation Humans Protein Structure, Tertiary RecQ Helicases Recombinant Fusion Proteins/analysis,isolation & purification Recombination, Genetic Repetitive Sequences, Nucleic Acid Telomere/chemistry,enzymology
Chemicals
DNA, Ribosomal Recombinant Fusion Proteins Adenosine Triphosphatases Bloom syndrome protein DNA Helicases RecQ Helicases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Schawalder James
Laboratory of Molecular Genetics, New York Blood Center, New York, New York 10021, USA. [email protected]
Paric Enesa
Neff Norma F
References (57)
57 references, click to expand
  1. Localization of the Bloom syndrome helicase to punctate nuclear structures and the nuclear matrix and regulation during the cell cycle: comparison with the Werner's syndrome helicase.
    Mol Carcinog. 1999 Dec;26(4):261-73 PMID: 10569803
  2. Pondering the promyelocytic leukemia protein (PML) puzzle: possible functions for PML nuclear bodies.
    Mol Cell Biol. 2002 Aug;22(15):5259-69 PMID: 12101223
  3. The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins.
    Structure. 1999 Dec 15;7(12):1557-66 PMID: 10647186
  4. Association of the Bloom syndrome protein with topoisomerase IIIalpha in somatic and meiotic cells.
    Cancer Res. 2000 Mar 1;60(5):1162-7 PMID: 10728666
  5. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.
    Genes Dev. 2000 Apr 15;14(8):927-39 PMID: 10783165
  6. The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability.
    BMC Cell Biol. 2001;2:11 PMID: 11472631
  7. Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases.
    J Biol Chem. 2002 Oct 25;277(43):41110-9 PMID: 12181313
  8. The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis.
    Hum Mol Genet. 2002 Dec 1;11(25):3135-44 PMID: 12444098
  9. The nonmutagenic repair of broken replication forks via recombination.
    Mutat Res. 2002 Dec 29;510(1-2):107-20 PMID: 12459447
  10. Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing.
    Science. 2003 Jan 10;299(5604):265-7 PMID: 12522255
  11. The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants.
    Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8193-8 PMID: 12826610
  12. Analysis of the replication pattern of Chinese hamster chromosomes using 5-bromodeoxyuridine suppression of 33258 Hoechst fluorescence.
    Chromosoma. 1975 Dec 10;53(3):209-21 PMID: 53132
  13. Localization by Q-banding of mitotic chiasmata in cases of Bloom's syndrome.
    Chromosoma. 1976 Aug 4;57(1):1-11 PMID: 954549
  14. Mitotic recombination and segregation of satellites in Bloom's syndrome.
    Chromosoma. 1981;82(5):627-36 PMID: 7261713
  15. Mitotic chiasmata, gene density, and oncogenes.
    Hum Genet. 1985;70(1):1-5 PMID: 3997147
  16. Molecular evidence that homologous recombination occurs in proliferating human somatic cells.
    Proc Natl Acad Sci U S A. 1990 Jun;87(11):4315-9 PMID: 1971948
  17. Chromatin structure and transcription.
    Annu Rev Cell Biol. 1992;8:563-87 PMID: 1335747
  18. Initiation and termination of DNA replication in human rRNA genes.
    Mol Cell Biol. 1993 Oct;13(10):6600-13 PMID: 8413256
  19. Bloom syndrome: a mendelian prototype of somatic mutational disease.
    Medicine (Baltimore). 1993 Nov;72(6):393-406 PMID: 8231788
  20. The Bloom's syndrome gene product is homologous to RecQ helicases.
    Cell. 1995 Nov 17;83(4):655-66 PMID: 7585968
  21. Structure, subnuclear distribution, and nuclear matrix association of the mammalian telomeric complex.
    J Cell Biol. 1996 Nov;135(4):867-81 PMID: 8922373
  22. BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal.
    Biochem Biophys Res Commun. 1997 Nov 17;240(2):348-53 PMID: 9388480
  23. Telomeres, the nucleolus and aging.
    Curr Opin Cell Biol. 1998 Jun;10(3):332-8 PMID: 9640533
  24. Structure, organization, and dynamics of promyelocytic leukemia protein nuclear bodies.
    Am J Hum Genet. 1998 Aug;63(2):297-304 PMID: 9683622
  25. The Bloom's syndrome helicase unwinds G4 DNA.
    J Biol Chem. 1998 Oct 16;273(42):27587-92 PMID: 9765292
  26. The DNA helicase activity of BLM is necessary for the correction of the genomic instability of bloom syndrome cells.
    Mol Biol Cell. 1999 Mar;10(3):665-76 PMID: 10069810
  27. Differences in the localization and morphology of chromosomes in the human nucleus.
    J Cell Biol. 1999 Jun 14;145(6):1119-31 PMID: 10366586
  28. DNA recombination: the replication connection.
    Trends Biochem Sci. 1999 Jul;24(7):271-5 PMID: 10390616
  29. PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1.
    J Cell Biol. 1999 Oct 18;147(2):221-34 PMID: 10525530
  30. Late DNA synthesis in heterochromatin.
    Nature. 1968 Jan 13;217(5124):138-42 PMID: 18300398
  31. Telomeres and telomerase in aging and cancer.
    Curr Opin Genet Dev. 1995 Apr;5(2):249-55 PMID: 7613096
  32. Nuclear structure in normal and Bloom syndrome cells.
    Proc Natl Acad Sci U S A. 2000 May 9;97(10):5214-9 PMID: 10779560
  33. Review: properties and assembly mechanisms of ND10, PML bodies, or PODs.
    J Struct Biol. 2000 Apr;129(2-3):278-87 PMID: 10806078
  34. Nijmegen breakage syndrome disease protein and MRE11 at PML nuclear bodies and meiotic telomeres.
    Cancer Res. 2000 May 1;60(9):2331-4 PMID: 10811102
  35. The Bloom's syndrome gene product promotes branch migration of holliday junctions.
    Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6504-8 PMID: 10823897
  36. Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase.
    Oncogene. 2000 May 25;19(23):2731-8 PMID: 10851073
  37. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres.
    Nat Genet. 2000 Jul;25(3):347-52 PMID: 10888888
  38. Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity.
    J Biol Chem. 2000 Aug 4;275(31):23500-8 PMID: 10825162
  39. The function of Xenopus Bloom's syndrome protein homolog (xBLM) in DNA replication.
    Genes Dev. 2000 Oct 15;14(20):2570-5 PMID: 11040210
  40. Binding and melting of D-loops by the Bloom syndrome helicase.
    Biochemistry. 2000 Nov 28;39(47):14617-25 PMID: 11087418
  41. Genome-wide location and function of DNA binding proteins.
    Science. 2000 Dec 22;290(5500):2306-9 PMID: 11125145
  42. SGS1, the Saccharomyces cerevisiae homologue of BLM and WRN, suppresses genome instability and homeologous recombination.
    Nat Genet. 2001 Jan;27(1):113-6 PMID: 11138010
  43. The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase.
    EMBO J. 2001 Feb 15;20(4):905-13 PMID: 11179234
  44. Chromosome territories, nuclear architecture and gene regulation in mammalian cells.
    Nat Rev Genet. 2001 Apr;2(4):292-301 PMID: 11283701
  45. Regulation and localization of the Bloom syndrome protein in response to DNA damage.
    J Cell Biol. 2001 Apr 16;153(2):367-80 PMID: 11309417
  46. Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51.
    J Biol Chem. 2001 Jun 1;276(22):19375-81 PMID: 11278509
  47. A new spectrin, beta IV, has a major truncated isoform that associates with promyelocytic leukemia protein nuclear bodies and the nuclear matrix.
    J Biol Chem. 2001 Jun 29;276(26):23974-85 PMID: 11294830
  48. The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases.
    Nucleic Acids Res. 2001 Jul 1;29(13):2843-9 PMID: 11433031
  49. Bacteriophage T4 gene 41 helicase and gene 59 helicase-loading protein: a versatile couple with roles in replication and recombination.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8312-8 PMID: 11459969
  50. The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair.
    J Biol Chem. 2001 Aug 10;276(32):30031-5 PMID: 11325959
  51. Protection of mammalian telomeres.
    Oncogene. 2002 Jan 21;21(4):532-40 PMID: 11850778
  52. New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin.
    Oncogene. 2002 Jan 21;21(4):553-63 PMID: 11850780
  53. Human DNA polymerase epsilon colocalizes with proliferating cell nuclear antigen and DNA replication late, but not early, in S phase.
    J Biol Chem. 2002 Mar 8;277(10):8658-66 PMID: 11741962
  54. Bloom's syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest.
    J Cell Biol. 2002 Apr 1;157(1):19-30 PMID: 11916980
  55. Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins.
    J Biol Chem. 2002 Jun 14;277(24):22035-44 PMID: 11919194
  56. Stabilized viral nucleic acids in plasma as an alternative shipping method for NAT.
    Transfusion. 2002 Apr;42(4):409-13 PMID: 12076286
  57. RecQ and RecJ process blocked replication forks prior to the resumption of replication in UV-irradiated Escherichia coli.
    Mol Gen Genet. 1999 Oct;262(3):543-51 PMID: 10589843
Article Info
Journal
BMC cell biology
Abbr.
BMC Cell Biol
ISSN
1471-2121
DOI
10.1186/1471-2121-4-15
Email
[email protected]
Published
2003-10-27
Epub
2003-00-27
Pages
15
Language
English
Region
England
NLM ID
100966972
PMCID
PMC270065
Subset
IM
External Links
PubMed source DOI: 10.1186/1471-2121-4-15 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2