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The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants

Imamura, Osamu and Campbell, Judith L. (2003) The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants. Proceedings of the National Academy of Sciences of the United States of America, 100 (14). pp. 8193-8198. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:IMApnas03

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Abstract

Bloom syndrome is a disorder of profound and early cancer predisposition in which cells become hypermutable, exhibit high frequency of sister chromatid exchanges, and show increased micronuclei. BLM, the gene mutated in Bloom syndrome, has been cloned previously, and the BLM protein is a member of the RecQ family of DNA helicases. Many lines of evidence suggest that BLM is involved either directly in DNA replication or in surveillance during DNA replication, but its specific roles remain unknown. Here we show that hBLM can suppress both the temperature-sensitive growth defect and the DNA damage sensitivity of the yeast DNA replication mutant dna2-1. The dna2-1 mutant is defective in a helicase-nuclease that is required either to coordinate with the crucial Saccharomyces cerevisiae (sc) FEN1 nuclease in Okazaki fragment maturation or to compensate for scFEN1 when its activity is impaired. We show that human BLM interacts with both scDna2 and scFEN1 by using coimmunoprecipitation from yeast extracts, suggesting that human BLM participates in the same steps of DNA replication or repair as scFEN1 and scDna2.


Item Type:Article
Additional Information:Copyright © 2003 by the National Academy of Sciences. Edited by Charles C. Richardson, Harvard Medical School, Boston, MA, and approved May 6, 2003 (received for review March 20, 2003). This paper was submitted directly (Track II) to the PNAS office. We thank Dr. Norma Neff for hBLM gene alleles and anti-hBLM antibody and for critical reading of the manuscript; Alexander Varshavsky for critical reading of the manuscript; Dr. Y. Furuichi for hBLM, mWRN, and hRECQ4 genes; and N. Nobuo for the hDNA2 EST clone. This work was supported by U.S. Public Health Service Grant GM25508.
Subject Keywords:SACCHAROMYCES-CEREVISIAE DNA2, OKAZAKI FRAGMENT MATURATION, S-PHASE, RECQ HELICASES, GENOMIC INSTABILITY, TOPOISOMERASE-III, G4 DNA, INTERACTS, HOMOLOG, SGS1
Record Number:CaltechAUTHORS:IMApnas03
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:IMApnas03
Alternative URL:http://dx.doi.org/10.1073/pnas.1431624100
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:932
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:09 Nov 2005
Last Modified:26 Dec 2012 08:42

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