|
|
||||||||
Original Article |
BACKGROUND: Bloom's syndrome (BS) is an autosomal recessive disorder causing short stature, immunodeficiency, and an increased risk of cancer. Increased rates of sister chromatid exchange and chromosomal aberration have been observed in cells having defects in the BLM gene. Among five kinds of human RecQ helicases cloned, the mutations in WRN and RecQL4 have been known as the causes of premature ageing. Little is, however, known about the function of BLM helicase in ageing. RESULTS: We show that human BLM, but not WRN can prevent the premature ageing and the increased homologous recombination at the rDNA loci caused by sgs1 mutation. Unexpectedly, the levels of ERCs (extrachromosomal rDNA circles), the products of homologous recombination, formed in 7-generation cells of the wild-type or the sgs1:BLM strain were comparable with those of the sgs1 or the sgs1:WRN age-matched-old cells. CONCLUSION: These results imply that BLM helicase may have an important role in human ageing. In addition, these data suggest that the accumulated ERCs per se may be not the cause of premature ageing in yeast, inconsistent with the model proposed by Sinclair & Guarente. We discuss a new model, which explains how Sgs1 or BLM helicase suppresses premature ageing in yeast.
This article has been cited by other articles:
![]() |
W. C. Burhans and M. Weinberger DNA replication stress, genome instability and aging Nucleic Acids Res., December 3, 2007; 35(22): 7545 - 7556. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Cobb and L. Bjergbaek RecQ helicases: lessons from model organisms Nucleic Acids Res., September 10, 2006; 34(15): 4106 - 4114. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Caburet, C. Conti, C. Schurra, R. Lebofsky, S. J. Edelstein, and A. Bensimon Human ribosomal RNA gene arrays display a broad range of palindromic structures Genome Res., August 1, 2005; 15(8): 1079 - 1085. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Lillard-Wetherell, K. A. Combs, and J. Groden BLM Helicase Complements Disrupted Type II Telomere Lengthening in Telomerase-Negative sgs1 Yeast Cancer Res., July 1, 2005; 65(13): 5520 - 5522. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Borghouts, A. Benguria, J. Wawryn, and S. M. Jazwinski Rtg2 Protein Links Metabolism and Genome Stability in Yeast Longevity Genetics, February 1, 2004; 166(2): 765 - 777. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. J. Bitterman, O. Medvedik, and D. A. Sinclair Longevity Regulation in Saccharomyces cerevisiae: Linking Metabolism, Genome Stability, and Heterochromatin Microbiol. Mol. Biol. Rev., September 1, 2003; 67(3): 376 - 399. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Imamura and J. L. Campbell The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants PNAS, July 8, 2003; 100(14): 8193 - 8198. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Takeuchi, T. Horiuchi, and T. Kobayashi Transcription-dependent recombination and the role of fork collision in yeast rDNA Genes & Dev., June 15, 2003; 17(12): 1497 - 1506. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Maftahi, J. C. Hope, L. Delgado-Cruzata, C. S. Han, and G. A. Freyer The severe slow growth of {Delta}srs2{Delta}rqh1 in Schizosaccharomyces pombe is suppressed by loss of recombination and checkpoint genes Nucleic Acids Res., October 15, 2002; 30(21): 4781 - 4792. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. L. M. Hoopes, M. Budd, W. Choe, T. Weitao, and J. L. Campbell Mutations in DNA Replication Genes Reduce Yeast Life Span Mol. Cell. Biol., June 15, 2002; 22(12): 4136 - 4146. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. W. Mankouri, T. J. Craig, and A. Morgan SGS1 is a multicopy suppressor of srs2: functional overlap between DNA helicases Nucleic Acids Res., March 1, 2002; 30(5): 1103 - 1113. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. J. Merker and H. L. Klein hpr1{Delta} Affects Ribosomal DNA Recombination and Cell Life Span in Saccharomyces cerevisiae Mol. Cell. Biol., January 15, 2002; 22(2): 421 - 429. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Pedrazzi, C. Perrera, H. Blaser, P. Kuster, G. Marra, S. L. Davies, G.-H. Ryu, R. Freire, I. D. Hickson, J. Jiricny, et al. Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1 Nucleic Acids Res., November 1, 2001; 29(21): 4378 - 4386. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Kaliraman, J. R. Mullen, W. M. Fricke, S. A. Bastin-Shanower, and S. J. Brill Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease Genes & Dev., October 15, 2001; 15(20): 2730 - 2740. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Kaeberlein, M. McVey, and L. Guarente Using Yeast to Discover the Fountain of Youth Sci. Aging Knowl. Environ., October 3, 2001; 2001(1): pe1 - 1. [Abstract] [Full Text] |
||||
![]() |
M. Bryk, M. Banerjee, D. Conte Jr., and M. J. Curcio The Sgs1 Helicase of Saccharomyces cerevisiae Inhibits Retrotransposition of Ty1 Multimeric Arrays Mol. Cell. Biol., August 15, 2001; 21(16): 5374 - 5388. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Wu and N. Maizels Substrate-specific inhibition of RecQ helicase Nucleic Acids Res., April 15, 2001; 29(8): 1765 - 1771. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. McVey, M. Kaeberlein, H. A. Tissenbaum, and L. Guarente The Short Life Span of Saccharomyces cerevisiae sgs1 and srs2 Mutants Is a Composite of Normal Aging Processes and Mitotic Arrest Due to Defective Recombination Genetics, April 1, 2001; 157(4): 1531 - 1542. [Abstract] [Full Text] |
||||
![]() |
L. WU, S.L. DAVIES, and I.D. HICKSON Roles of RecQ Family Helicases in the Maintenance of Genome Stability Cold Spring Harb Symp Quant Biol, January 1, 2000; 65(0): 573 - 582. [Abstract] [PDF] |
||||
![]() |
R. J. Bennett, M.-F. Noirot-Gros, and J. C. Wang Interaction between Yeast Sgs1 Helicase and DNA Topoisomerase III J. Biol. Chem., August 25, 2000; 275(35): 26898 - 26905. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. M. Fricke, V. Kaliraman, and S. J. Brill Mapping the DNA Topoisomerase III Binding Domain of the Sgs1 DNA Helicase J. Biol. Chem., March 16, 2001; 276(12): 8848 - 8855. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | ADVANCED SEARCH | TABLE OF CONTENTS |