Title

Recovery from DNA damage-induced G(2) arrest requires actin-binding protein filamin-A/actin-binding protein 280

Document Type

Article

Peer Reviewed

1

Publication Date

2-1-2004

NLM Title Abbreviation

J Biol Chem

Journal/Book/Conference Title

Journal of Biological Chemistry

DOI of Published Version

10.1074/jbc.M306794200

Abstract

Filamin-A (filamin-1) is an actin-binding protein involved in the organization of actin networks. Our previous study shows that filamin-A interacts with BRCA2, and lack of filamin-A expression results in increased cellular sensitivity to several DNA damaging agents in melanoma cells (Yuan, Y., and Shen, Z. (2001) J. Biol. Chem. 276, 48318-48324), suggesting a role of filamin-A in DNA damage response. In this report, we demonstrated that deficiency of filamin-A results in an 8-h delay in the recovery from G(2) arrest in response to ionizing radiation. However, filamin-A deficiency does not affect the initial activation of the G(2)/M checkpoint. We also found that filamin-A deficiency results in sustained activation of Chk1 and Chk2 after irradiation. This in turn causes a delay in the dephosphorylation of phospho-Cdc2, which is inhibitory to the G(2)/M transition. In addition, filamin-A-deficient M2 cells undergo mitotic catastrophe-related nuclear fragmentation after they are released from the G(2) arrest. Together, these data suggest a functional role of filamin-A in the recovery from G(2) arrest and subsequent mitotic cell death after DNA damage.

Published Article/Book Citation

Journal of Biological Chemistry, 279:7 (2004) pp.6098-6105.

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URL

http://ir.uiowa.edu/obgyn_pubs/503