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


RESULTS
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.


CONCLUSIONS
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.
Schawalder
James
J
Laboratory of Molecular Genetics, New York Blood Center, New York, New York 10021, USA. jschawalder@helicontherapeutics.com
Paric
Enesa
E
Neff
Norma F
NF
D000251:Adenosine Triphosphatases / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D000483:Alleles; D001665:Binding Sites; D001816:Bloom Syndrome / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D002453:Cell Cycle; D002460:Cell Line; D002466:Cell Nucleolus / Q000201:enzymology; D022003:Cell Nucleus Structures / Q000201:enzymology; D002875:Chromosomes / Q000201:enzymology* / Q000648:ultrastructure; D004265:DNA Helicases / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D004275:DNA, Ribosomal / Q000032:analysis / Q000737:chemistry*; D014644:Genetic Variation; D006801:Humans; D017434:Protein Structure, Tertiary; D053484:RecQ Helicases; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000302:isolation & purification; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000737:chemistry* / Q000201:enzymology
D004275:DNA, Ribosomal; D011993:Recombinant Fusion Proteins; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases