Physical and functional interaction between the Bloom's syndrome gene product and the largest subunit of chromatin assembly factor 1.
Bloom's syndrome (BS) is a genomic instability disorder characterized by cancer susceptibility. The protein defective in BS, BLM, belongs to the RecQ family of DNA helicases. In this study, we found that BLM interacts with hp150, the largest subunit of chromatin assembly factor 1 (CAF-1), in vitro and in vivo. Colocalization of a proportion of the cellular complement of these two proteins is found at specific nuclear foci coinciding with sites of DNA synthesis in the S phase. This colocalization increases in the presence of agents that damage DNA or inhibit DNA replication. In support of a functional interaction between BLM and CAF-1, we show that BLM inhibits CAF-1-mediated chromatin assembly during DNA repair in vitro. Although CAF-1 activity is not altered in BLM-deficient cells, the absence of BLM does impair the ability of CAF-1 to be mobilized within the nucleus in response to hydroxyurea treatment. Our results provide the first link between BLM and chromatin assembly coupled to DNA repair and suggest that BLM and CAF-1 function in a coordinated way to promote survival in response to DNA damage and/or replication blockade.
Jiao
Renjie
R
Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurstr. 190, CH-8057 Zürich, Switzerland.
Bachrati
Csanád Z
CZ
Pedrazzi
Graziella
G
Kuster
Patrick
P
Petkovic
Maja
M
Li
Ji-Liang
JL
Egli
Dieter
D
Hickson
Ian D
ID
Stagljar
Igor
I
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D025941:Protein Interaction Mapping; D053484:RecQ Helicases
C533593:CHAF1B protein, human; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases