Bloom's syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest

doi:10.1083/jcb.200110009

Published online 26 March 2002. doi:10.1083/jcb.200110009

This Article

	Full Text
	Full Text (PDF, 571K)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Franchitto, A.
	Articles by Pichierri, P.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Franchitto, A.
	Articles by Pichierri, P.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/2002/4/19 $5.00
The Journal of Cell Biology, Volume 157, Number 1, April 1, 2002 19-30

Article

Bloom's syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest

Annapaola Franchitto and Pietro Pichierri

Laboratorio di Citogenetica Molecolare e Mutagenesi, DABAC, Università della Tuscia, 01100 Viterbo, Italy

Address correspondence to Pietro Pichierri, 94801 Villejuif, France. Tel.: 33-1-4958-3409. Fax: 33-1-4958-3411. E-mail: pichier{at}vjf.cnrs.fr

Bloom's syndrome (BS) is a rare genetic disorder characterizedby a broad range of symptoms and, most importantly, a predispositionto many types of cancers. Cells derived from patients with BSexhibit an elevated rate of somatic recombination and hypermutability,supporting a role for bleomycin (BLM) in the maintenance ofgenomic integrity. BLM is thought to participate in severalDNA transactions, the failure of which could give raise to genomicinstability, and to interact with many proteins involved inreplication, recombination, and repair. In this study, we showthat BLM function is specifically required to properly relocalizethe RAD50/MRE11/NBS1 (RMN) complex at sites of replication arrest,but is not essential in the activation of BRCA1 either afterstalled replication forks or ${gamma}$ -rays. We also provide evidencethat BLM is phosphorylated after replication arrest in an Ataxiaand RAD3-related protein (ATR)-dependent manner and that phosphorylationis not required for subnuclear relocalization. Therefore, inATR dominant negative mutant cells, the assembly of the RMNcomplex in nuclear foci after replication blockage is almostcompletely abolished. Together, these results suggest a relationshipbetween BLM, ATR, and the RMN complex in the response to replicationarrest, proposing a role for BLM protein and RMN complex inthe resolution of stalled replication forks.

Key Words: BLM; RecQ helicases; replication arrest; recombination; MRE11

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Grillari, J., Katinger, H., Voglauer, R. (2007). Contributions of DNA interstrand cross-links to aging of cells and organisms. Nucleic Acids Res 0: gkm1065v1-gkm1065 [Abstract] [Full Text]
Olson, E., Nievera, C. J., Lee, A. Y.-L., Chen, L., Wu, X. (2007). The Mre11-Rad50-Nbs1 Complex Acts Both Upstream and Downstream of Ataxia Telangiectasia Mutated and Rad3-related Protein (ATR) to Regulate the S-phase Checkpoint following UV Treatment. J. Biol. Chem. 282: 22939-22952 [Abstract] [Full Text]
Johnson-Schlitz, D., Engels, W. R. (2006). Template disruptions and failure of double Holliday junction dissolution during double-strand break repair in Drosophila BLM mutants. Proc. Natl. Acad. Sci. USA 103: 16840-16845 [Abstract] [Full Text]
Cohen, P. E., Pollack, S. E., Pollard, J. W. (2006). Genetic Analysis of Chromosome Pairing, Recombination, and Cell Cycle Control during First Meiotic Prophase in Mammals. Endocr. Rev. 27: 398-426 [Abstract] [Full Text]
Sobeck, A., Stone, S., Costanzo, V., de Graaf, B., Reuter, T., de Winter, J., Wallisch, M., Akkari, Y., Olson, S., Wang, W., Joenje, H., Christian, J. L., Lupardus, P. J., Cimprich, K. A., Gautier, J., Hoatlin, M. E. (2006). Fanconi Anemia Proteins Are Required To Prevent Accumulation of Replication-Associated DNA Double-Strand Breaks. Mol. Cell. Biol. 26: 425-437 [Abstract] [Full Text]
Rao, V. A., Fan, A. M., Meng, L., Doe, C. F., North, P. S., Hickson, I. D., Pommier, Y. (2005). Phosphorylation of BLM, Dissociation from Topoisomerase III{alpha}, and Colocalization with {gamma}-H2AX after Topoisomerase I-Induced Replication Damage. Mol. Cell. Biol. 25: 8925-8937 [Abstract] [Full Text]
Zhang, J., Powell, S. N. (2005). The Role of the BRCA1 Tumor Suppressor in DNA Double-Strand Break Repair. Mol Cancer Res 3: 531-539 [Abstract] [Full Text]
Chiolo, I., Carotenuto, W., Maffioletti, G., Petrini, J. H. J., Foiani, M., Liberi, G. (2005). Srs2 and Sgs1 DNA Helicases Associate with Mre11 in Different Subcomplexes following Checkpoint Activation and CDK1-Mediated Srs2 Phosphorylation. Mol. Cell. Biol. 25: 5738-5751 [Abstract] [Full Text]
Fagundes, M. R. v. Z. K., Semighini, C. P., Malavazi, I., Savoldi, M., de Lima, J. F., de Souza Goldman, M. H., Harris, S. D., Goldman, G. H. (2005). Aspergillus nidulans uvsBATR and scaANBS1 Genes Show Genetic Interactions during Recovery from Replication Stress and DNA Damage. Eukaryot Cell 4: 1239-1252 [Abstract] [Full Text]
Eladad, S., Ye, T.-Z., Hu, P., Leversha, M., Beresten, S., Matunis, M. J., Ellis, N. A. (2005). Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification. Hum Mol Genet 14: 1351-1365 [Abstract] [Full Text]
Jurvansuu, J., Raj, K., Stasiak, A., Beard, P. (2005). Viral Transport of DNA Damage That Mimics a Stalled Replication Fork. J. Virol. 79: 569-580 [Abstract] [Full Text]
Sengupta, S., Robles, A. I., Linke, S. P., Sinogeeva, N. I., Zhang, R., Pedeux, R., Ward, I. M., Celeste, A., Nussenzweig, A., Chen, J., Halazonetis, T. D., Harris, C. C. (2004). Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. JCB 166: 801-813 [Abstract] [Full Text]
Puizina, J., Siroky, J., Mokros, P., Schweizer, D., Riha, K. (2004). Mre11 Deficiency in Arabidopsis Is Associated with Chromosomal Instability in Somatic Cells and Spo11-Dependent Genome Fragmentation during Meiosis. Plant Cell 16: 1968-1978 [Abstract] [Full Text]
Li, W., Kim, S.-M., Lee, J., Dunphy, W. G. (2004). Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases. JCB 165: 801-812 [Abstract] [Full Text]
Taylor, T. J., Knipe, D. M. (2004). Proteomics of Herpes Simplex Virus Replication Compartments: Association of Cellular DNA Replication, Repair, Recombination, and Chromatin Remodeling Proteins with ICP8. J. Virol. 78: 5856-5866 [Abstract] [Full Text]
Jiao, R., Bachrati, C. Z., Pedrazzi, G., Kuster, P., Petkovic, M., Li, J.-L., Egli, D., Hickson, I. D., Stagljar, I. (2004). Physical and Functional Interaction between the Bloom's Syndrome Gene Product and the Largest Subunit of Chromatin Assembly Factor 1. Mol. Cell. Biol. 24: 4710-4719 [Abstract] [Full Text]
Cheng, W.-H., von Kobbe, C., Opresko, P. L., Arthur, L. M., Komatsu, K., Seidman, M. M., Carney, J. P., Bohr, V. A. (2004). Linkage between Werner Syndrome Protein and the Mre11 Complex via Nbs1. J. Biol. Chem. 279: 21169-21176 [Abstract] [Full Text]
Opresko, P. L., Cheng, W.-H., Bohr, V. A. (2004). Junction of RecQ Helicase Biochemistry and Human Disease. J. Biol. Chem. 279: 18099-18102 [Full Text]
Warren, C. D., Eckley, D. M., Lee, M. S., Hanna, J. S., Hughes, A., Peyser, B., Jie, C., Irizarry, R., Spencer, F. A. (2004). S-Phase Checkpoint Genes Safeguard High-Fidelity Sister Chromatid Cohesion. Mol. Biol. Cell 15: 1724-1735 [Abstract] [Full Text]
Davies, S. L., North, P. S., Dart, A., Lakin, N. D., Hickson, I. D. (2004). Phosphorylation of the Bloom's Syndrome Helicase and Its Role in Recovery from S-Phase Arrest. Mol. Cell. Biol. 24: 1279-1291 [Abstract] [Full Text]
Yang, J., Yu, Y., Hamrick, H. E., Duerksen-Hughes, P. J. (2003). ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses. Carcinogenesis 24: 1571-1580 [Abstract] [Full Text]
Davalos, A. R., Campisi, J. (2003). Bloom syndrome cells undergo p53-dependent apoptosis and delayed assembly of BRCA1 and NBS1 repair complexes at stalled replication forks. JCB 162: 1197-1209 [Abstract] [Full Text]
Zhao, S., Renthal, W., Lee, E. Y.-H. P. (2002). Functional analysis of FHA and BRCT domains of NBS1 in chromatin association and DNA damage responses. Nucleic Acids Res 30: 4815-4822 [Abstract] [Full Text]
Franchitto, A., Pichierri, P. (2002). Protecting genomic integrity during DNA replication: correlation between Werner's and Bloom's syndrome gene products and the MRE11 complex. Hum Mol Genet 11: 2447-2453 [Abstract] [Full Text]
Beamish, H., Kedar, P., Kaneko, H., Chen, P., Fukao, T., Peng, C., Beresten, S., Gueven, N., Purdie, D., Lees-Miller, S., Ellis, N., Kondo, N., Lavin, M. F. (2002). Functional Link between BLM Defective in Bloom's Syndrome and the Ataxia-telangiectasia-mutated Protein, ATM. J. Biol. Chem. 277: 30515-30523 [Abstract] [Full Text]