Journal article
Recovery from DNA Damage-induced G sub(2) Arrest Requires Actin-binding Protein Filamin-A/Actin-binding Protein 280
Journal of Biological Chemistry, Vol.279(7), pp.6098-6105
02/13/2004
DOI: 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 sub(2) arrest in response to ionizing radiation. However, filamin-A deficiency does not affect the initial activation of the G sub(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 sub(2)/M transition. In addition, filamin-A- deficient M2 cells undergo mitotic catastrophe-related nuclear fragmentation after they are released from the G sub(2) arrest. Together, these data suggest a functional role of filamin-A in the recovery from G sub(2) arrest and subsequent mitotic cell death after DNA damage.
Details
- Title: Subtitle
- Recovery from DNA Damage-induced G sub(2) Arrest Requires Actin-binding Protein Filamin-A/Actin-binding Protein 280
- Creators
- Xiangbing Meng - University of Iowa, PathologyYuan Yuan - University of New MexicoAdrian MaestasZhiyuan Shen
- Resource Type
- Journal article
- Publication Details
- Journal of Biological Chemistry, Vol.279(7), pp.6098-6105
- DOI
- 10.1074/jbc.M306794200
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Language
- English
- Date published
- 02/13/2004
- Academic Unit
- Pathology
- Record Identifier
- 9983557404102771
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