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First published online 19 April 2005
doi: 10.1242/jcs.02336

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53BP1 exchanges slowly at the sites of DNA damage and appears to require RNA for its association with chromatin

Fiona Pryde^1,*, Shirin Khalili^1,*, Kathryn Robertson¹, Jim Selfridge², Ann-Marie Ritchie², David W. Melton², Denis Jullien¹ and Yasuhisa Adachi^1,

¹ The Wellcome Trust Centre for Cell Biology, The Institute of Cell and Molecular Biology, The University of Edinburgh, The King's Buildings, Edinburgh, EH9 3JR, UK
² Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK

Author for correspondence (e-mail: y.adachi{at}ed.ac.uk)

Accepted 17 February 2005

53BP1 protein is re-localized to the sites of DNA damage after ionizing radiation (IR) and is involved in DNA-damage-checkpoint signal transduction. We examined the dynamics of GFP-53BP1 in living cells. The protein starts to accumulate at the sites of DNA damage 2-3 minutes after damage induction. Fluorescence recovery after photobleaching experiments showed that GFP-53BP1 is highly mobile in non-irradiated cells. Upon binding to the IR-induced nuclear foci, the mobility of 53BP1 reduces greatly. The minimum (M) domain of 53BP1 essential for targeting to IR induced foci consists of residues 1220-1703. GFP-M protein forms foci in mouse embryonic fibroblast cells lacking functional endogenous 53BP1. The M domain contains a tandem repeat of Tudor motifs and an arginine- and glycine-rich domain (RG stretch), which are often found in proteins involved in RNA metabolism, the former being essential for targeting. RNase A treatment dissociates 53BP1 from IR-induced foci. In HeLa cells, dissociation of the M domain without the RG stretch by RNase A treatment can be restored by re-addition of nuclear RNA in the early stages of post-irradiation. 53BP1 immunoprecipitates contain some RNA molecules. Our results suggest a possible involvement of RNA in the binding of 53BP1 to chromatin damaged by IR.

Key words: 53BP1, Ionizing radiation, DNA damage, FRAP, RNA

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