DOI: 10.1083/jcb.200110009. Bloom's syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest

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

10.1083/jcb.200110009

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Bloom's syndrome (BS) is a rare genetic disorder characterized by a broad range of symptoms and, most importantly, a predisposition to many types of cancers. Cells derived from patients with BS exhibit an elevated rate of somatic recombination and hypermutability, supporting a role for bleomycin (BLM) in the maintenance of genomic integrity. BLM is thought to participate in several DNA transactions, the failure of which could give raise to genomic instability, and to interact with many proteins involved in replication, recombination, and repair. In this study, we show that BLM function is specifically required to properly relocalize the RAD50/MRE11/NBS1 (RMN) complex at sites of replication arrest, but is not essential in the activation of BRCA1 either after stalled replication forks or γ-rays. We also provide evidence that BLM is phosphorylated after replication arrest in an Ataxia and RAD3-related protein (ATR)-dependent manner and that phosphorylation is not required for subnuclear relocalization. Therefore, in ATR dominant negative mutant cells, the assembly of the RMN complex in nuclear foci after replication blockage is almost completely abolished. Together, these results suggest a relationship between BLM, ATR, and the RMN complex in the response to replication arrest, proposing a role for BLM protein and RMN complex in the resolution of stalled replication forks.

Bibliography

Franchitto, A., & Pichierri, P. (2002). Bloomâs syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest. The Journal of Cell Biology, 157(1), 19â30.

Authors 2

Annapaola Franchitto (first)
Pietro Pichierri (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:46 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 9:29 a.m.)
Indexed	3 months ago (May 24, 2025, 3:26 a.m.)
Issued	23 years, 5 months ago (March 26, 2002)
Published	23 years, 5 months ago (March 26, 2002)
Published Online	23 years, 5 months ago (March 26, 2002)
Published Print	23 years, 4 months ago (April 1, 2002)

Funders 0

None

BibTeX

@article{Franchitto_2002, title={Bloom’s syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest}, volume={157}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200110009}, DOI={10.1083/jcb.200110009}, number={1}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Franchitto, Annapaola and Pichierri, Pietro}, year={2002}, month=mar, pages={19–30} }

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