Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (60)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Hu, P.
Right arrow Articles by Ellis, N. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hu, P.
Right arrow Articles by Ellis, N. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2001, Vol. 10, No. 12 1287-1298
© 2001 Oxford University Press

Evidence for BLM and Topoisomerase III{alpha} interaction in genomic stability

Peng Hu, Sergey Beresten, Anja van Brabant, Tian-Zhang Ye, Pier-Paolo Pandolfi1, F. Brad Johnson2, Leonard Guarente2 and Nathan A. Ellis+

Laboratory of Cancer Susceptibility, Department of Human Genetics and the Cell Biology Program and 1Laboratory of Molecular and Developmental Biology, Department of Human Genetics and the Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA and 2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA

The genomic instability of persons with Bloom’s syndrome (BS) features particularly an increased number of sister-chromatid exchanges (SCEs). The primary cause of the genomic instability is mutation at BLM, which encodes a DNA helicase of the RecQ family. BLM interacts with Topoisomerase III{alpha} (Topo III{alpha}), and both BLM and Topo III{alpha} localize to the nuclear organelles referred to as the promyelocytic leukemia protein (PML) nuclear bodies. In this study we show, by analysis of cells that express various deletion constructs of green fluorescent protein (GFP)-tagged BLM, that the first 133 amino acids of BLM are necessary and sufficient for interaction between Topo III{alpha} and BLM. The Topo III{alpha}-interaction domain of BLM is not required for BLM’s localization to the PML nuclear bodies; in contrast, Topo III{alpha} is recruited to the PML nuclear bodies via its interaction with BLM. Expression of a full-length BLM (amino acids 1–1417) in BS cells can correct their high SCEs to normal levels, whereas expression of a BLM fragment that lacks the Topo III{alpha} interaction domain (amino acids 133–1417) results in intermediate SCE levels. The deficiency of amino acids 133–1417 in the reduction of SCEs was not explained by a defect in DNA helicase activity, because immunoprecipitated 133–1417 protein had 4-fold higher activity than GFP-BLM. The data implicate the BLM-Topo III{alpha} complex in the regulation of recombination in somatic cells.

+ To whom correspondence should be addressed at: Memorial Sloan-Kettering Cancer Center, Box 124, 1275 York Avenue, New York, NY 10021, USA; Tel: +1 212 639 7183; Fax: +1 212 717 3571; Email: n-ellis@ski.mskcc.org


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
V. Srivastava, P. Modi, V. Tripathi, R. Mudgal, S. De, and S. Sengupta
BLM helicase stimulates the ATPase and chromatin-remodeling activities of RAD54
J. Cell Sci., September 1, 2009; 122(17): 3093 - 3103.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
D. Xu, R. Guo, A. Sobeck, C. Z. Bachrati, J. Yang, T. Enomoto, G. W. Brown, M. E. Hoatlin, I. D. Hickson, and W. Wang
RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability
Genes & Dev., October 15, 2008; 22(20): 2843 - 2855.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
R. M. Brosh Jr and V. A. Bohr
Human premature aging, DNA repair and RecQ helicases
Nucleic Acids Res., December 3, 2007; 35(22): 7527 - 7544.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. Hartung, S. Suer, and H. Puchta
Two closely related RecQ helicases have antagonistic roles in homologous recombination and DNA repair in Arabidopsis thaliana
PNAS, November 20, 2007; 104(47): 18836 - 18841.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
V. A. Rao, C. Conti, J. Guirouilh-Barbat, A. Nakamura, Z.-H. Miao, S. L. Davies, B. Sacca, I. D. Hickson, A. Bensimon, and Y. Pommier
Endogenous {gamma}-H2AX-ATM-Chk2 Checkpoint Activation in Bloom's Syndrome Helicase Deficient Cells Is Related to DNA Replication Arrested Forks
Mol. Cancer Res., July 1, 2007; 5(7): 713 - 724.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
H. Babbe, N. Chester, P. Leder, and B. Reizis
The Bloom's Syndrome Helicase Is Critical for Development and Function of the {alpha}{beta} T-Cell Lineage
Mol. Cell. Biol., March 1, 2007; 27(5): 1947 - 1959.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
G. Dellaire, R. W. Ching, K. Ahmed, F. Jalali, K. C.K. Tse, R. G. Bristow, and D. P. Bazett-Jones
Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR
J. Cell Biol., October 9, 2006; 175(1): 55 - 66.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Ralf, I. D. Hickson, and L. Wu
The Bloom's Syndrome Helicase Can Promote the Regression of a Model Replication Fork
J. Biol. Chem., August 11, 2006; 281(32): 22839 - 22846.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Leng, D. W. Chan, H. Luo, C. Zhu, J. Qin, and Y. Wang
MPS1-dependent mitotic BLM phosphorylation is important for chromosome stability
PNAS, August 1, 2006; 103(31): 11485 - 11490.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. Condemine, Y. Takahashi, J. Zhu, F. Puvion-Dutilleul, S. Guegan, A. Janin, and H. de The
Characterization of endogenous human promyelocytic leukemia isoforms.
Cancer Res., June 15, 2006; 66(12): 6192 - 6198.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
J. J. Luciani, D. Depetris, Y. Usson, C. Metzler-Guillemain, C. Mignon-Ravix, M. J. Mitchell, A. Megarbane, P. Sarda, H. Sirma, A. Moncla, et al.
PML nuclear bodies are highly organised DNA-protein structures with a function in heterochromatin remodelling at the G2 phase
J. Cell Sci., June 15, 2006; 119(12): 2518 - 2531.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
V. A. Rao, A. M. Fan, L. Meng, C. F. Doe, P. S. North, I. D. Hickson, and Y. Pommier
Phosphorylation of BLM, Dissociation from Topoisomerase III{alpha}, and Colocalization with {gamma}-H2AX after Topoisomerase I-Induced Replication Damage
Mol. Cell. Biol., October 15, 2005; 25(20): 8925 - 8937.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Eladad, T.-Z. Ye, P. Hu, M. Leversha, S. Beresten, M. J. Matunis, and N. A. Ellis
Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification
Hum. Mol. Genet., May 15, 2005; 14(10): 1351 - 1365.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Hu, X. Lu, E. Barnes, M. Yan, H. Lou, and G. Luo
Recql5 and Blm RecQ DNA Helicases Have Nonredundant Roles in Suppressing Crossovers
Mol. Cell. Biol., May 1, 2005; 25(9): 3431 - 3442.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Zhang, S. Sengupta, Q. Yang, S. P. Linke, N. Yanaihara, J. Bradsher, V. Blais, C. H. McGowan, and C. C. Harris
BLM Helicase Facilitates Mus81 Endonuclease Activity in Human Cells
Cancer Res., April 1, 2005; 65(7): 2526 - 2531.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
W. Li, S.-M. Kim, J. Lee, and W. G. Dunphy
Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases
J. Cell Biol., June 21, 2004; 165(6): 801 - 812.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Cheng, C.-X. Zhu, C. Ji, A. Ahumada, and Y.-C. Tse-Dinh
Direct Interaction between Escherichia coli RNA Polymerase and the Zinc Ribbon Domains of DNA Topoisomerase I
J. Biol. Chem., August 15, 2003; 278(33): 30705 - 30710.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
W. M. Fricke and S. J. Brill
Slx1--Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1--Top3
Genes & Dev., July 15, 2003; 17(14): 1768 - 1778.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. R. Meetei, S. Sechi, M. Wallisch, D. Yang, M. K. Young, H. Joenje, M. E. Hoatlin, and W. Wang
A Multiprotein Nuclear Complex Connects Fanconi Anemia and Bloom Syndrome
Mol. Cell. Biol., May 15, 2003; 23(10): 3417 - 3426.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
D. J. Stavropoulos, P. S. Bradshaw, X. Li, I. Pasic, K. Truong, M. Ikura, M. Ungrin, and M. S. Meyn
The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis
Hum. Mol. Genet., December 1, 2002; 11(25): 3135 - 3144.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
L. Wu and I. D. Hickson
The Bloom's syndrome helicase stimulates the activity of human topoisomerase III{alpha}
Nucleic Acids Res., November 15, 2002; 30(22): 4823 - 4829.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Franchitto and P. Pichierri
Protecting genomic integrity during DNA replication: correlation between Werner's and Bloom's syndrome gene products and the MRE11 complex
Hum. Mol. Genet., October 1, 2002; 11(20): 2447 - 2453.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Wang, Y. L. Lyu, and J. C. Wang
Dual localization of human DNA topoisomerase IIIalpha to mitochondria and nucleus
PNAS, September 17, 2002; 99(19): 12114 - 12119.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. D. Huber, D. C. Lee, and N. Maizels
G4 DNA unwinding by BLM and Sgs1p: substrate specificity and substrate-specific inhibition
Nucleic Acids Res., September 15, 2002; 30(18): 3954 - 3961.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Wilson-Sali and T.-s. Hsieh
Generation of Double-stranded Breaks in Hypernegatively Supercoiled DNA by Drosophila Topoisomerase IIIbeta , a Type IA Enzyme
J. Biol. Chem., July 19, 2002; 277(30): 26865 - 26871.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
A. Franchitto and P. Pichierri
Bloom's syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest
J. Cell Biol., April 1, 2002; 157(1): 19 - 30.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
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]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. J. Bennett and J. C. Wang
Association of yeast DNA topoisomerase III and Sgs1 DNA helicase: Studies of fusion proteins
PNAS, September 5, 2001; (2001) 201387098.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. W. Wang, A. Tseng, N. A. Ellis, E. A. Spillare, S. P. Linke, A. I. Robles, H. Seker, Q. Yang, P. Hu, S. Beresten, et al.
Functional Interaction of p53 and BLM DNA Helicase in Apoptosis
J. Biol. Chem., August 24, 2001; 276(35): 32948 - 32955.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. J. Bennett and J. C. Wang
Association of yeast DNA topoisomerase III and Sgs1 DNA helicase: Studies of fusion proteins
PNAS, September 25, 2001; 98(20): 11108 - 11113.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
A. Franchitto and P. Pichierri
Bloom's syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest
J. Cell Biol., April 1, 2002; 157(1): 19 - 30.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.