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.
Skip Nav Destination
Article navigation
1 April 2002
Article|
March 26 2002
Bloom's syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest
Annapaola Franchitto,
Annapaola Franchitto
Laboratorio di Citogenetica Molecolare e Mutagenesi, DABAC, Università della Tuscia, 01100 Viterbo, Italy
Search for other works by this author on:
Pietro Pichierri
Pietro Pichierri
Laboratorio di Citogenetica Molecolare e Mutagenesi, DABAC, Università della Tuscia, 01100 Viterbo, Italy
Search for other works by this author on:
Annapaola Franchitto
Laboratorio di Citogenetica Molecolare e Mutagenesi, DABAC, Università della Tuscia, 01100 Viterbo, Italy
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: [email protected]
A. Franchitto and P. Pichierri's current address is CNRS UPR2169, Institut de Recherches sur le Cancer, Andrè Lwoff, 7, Rue Guy Moquet, 94801 Villejuif, France.
*
Abbreviations used in this paper: ATR, Ataxia and RAD3-related protein; BLM, BS protein; BrdUrd, 5′-bromo-2-deoxyuridine; BS, Bloom's syndrome; HU, hydroxyurea; RMN, RAD50/MRE11/NBS1; SCE, sister chromatid exchange; WS, Werner's syndrome.
Received:
October 02 2001
Revision Received:
January 14 2002
Accepted:
February 13 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 157 (1): 19–30.
Article history
Received:
October 02 2001
Revision Received:
January 14 2002
Accepted:
February 13 2002
Citation
Annapaola Franchitto, Pietro Pichierri; Bloom's syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest . J Cell Biol 1 April 2002; 157 (1): 19–30. doi: https://doi.org/10.1083/jcb.200110009
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement
Advertisement