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Potential role for 53BP1 in DNA end-joining repair through direct interaction with DNA

journal contribution
posted on 2023-06-08, 06:14 authored by Kuniyoshi Iwabuchi, Balaka Piku Basu, Boris Kysela, Takayuki Kurihara, Masao Shibata, Deyu Guan, Yongheng Cao, Tomio Hamada, Kouji Imamura, Penny Jeggo, Takayasu Date, Aidan DohertyAidan Doherty
Upon DNA damage, p53-binding protein 1 (53BP1) relocalizes to sites of DNA double-strand breaks and forms discrete nuclear foci, suggesting its role in DNA damage responses. We show that 53BP1 changed its localization from the detergent soluble to insoluble fraction after treatment of cells with x-ray, but not with ultraviolet or hydroxyurea. Either DNase or phosphatase treatment of the insoluble fraction released 53BP1 into the soluble fraction, showing that 53BP1 binds to chromatin in a phosphorylation-dependent manner after X-irradiation of cells. 53BP1 was retained at discrete nuclear foci in X-irradiated cells even after detergent extraction of cells, showing that the chromatin binding of 53BP1 occurs at sites of DNA double-strand breaks. The minimal domain for focus formation was identified by immunofluorescence staining of cells ectopically expressed with 53BP1 deletion mutants. This domain consisted of conserved Tudor and Myb motifs. The Tudor plus Myb domain possessed chromatin binding activity in vivo and bound directly to both double-stranded and single-stranded DNA in vitro. This domain also stimulated end-joining by DNA ligase IV/Xrcc4, but not by T4 DNA ligase in vitro. We conclude that 53BP1 has the potential to participate directly in the repair of DNA double-strand breaks.

History

Publication status

  • Published

Journal

Journal of Biological Chemistry

ISSN

0021-9258

Issue

38

Volume

278

Page range

36487-36495

Pages

9.0

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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