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Molecular and Cellular Biology, July 2008, p. 4620-4628, Vol. 28, No. 14
0270-7306/08/$08.00+0     doi:10.1128/MCB.02243-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

APLF (C2orf13) Is a Novel Component of Poly(ADP-Ribose) Signaling in Mammalian Cells{triangledown}

Stuart L. Rulten,{dagger} Felipe Cortes-Ledesma,{dagger} Liandi Guo, Natasha J. Iles, and Keith W. Caldecott*

Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, United Kingdom

Received 19 December 2007/ Returned for modification 4 February 2008/ Accepted 6 May 2008

APLF is a novel protein of unknown function that accumulates at sites of chromosomal DNA strand breakage via forkhead-associated (FHA) domain-mediated interactions with XRCC1 and XRCC4. APLF can also accumulate at sites of chromosomal DNA strand breaks independently of the FHA domain via an unidentified mechanism that requires a highly conserved C-terminal tandem zinc finger domain. Here, we show that the zinc finger domain binds tightly to poly(ADP-ribose), a polymeric posttranslational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. Protein poly(ADP-ribosyl)ation is tightly regulated and defects in either its synthesis or degradation slow global rates of chromosomal single-strand break repair. Interestingly, APLF negatively affects poly(ADP-ribosyl)ation in vitro, and this activity is dependent on its capacity to bind the polymer. In addition, transient overexpression in human A549 cells of full-length APLF or a C-terminal fragment encoding the tandem zinc finger domain greatly suppresses the appearance of poly(ADP-ribose), in a zinc finger-dependent manner. We conclude that APLF can accumulate at sites of chromosomal damage via zinc finger-mediated binding to poly(ADP-ribose) and is a novel component of poly(ADP-ribose) signaling in mammalian cells.

* Corresponding author. Mailing address: Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, United Kingdom. Phone: 44 (0) 1273 877519. Fax: 44 (0) 1273 678121. E-mail: k.w.caldecott{at}sussex.ac.uk

{triangledown} Published ahead of print on 12 May 2008.

{dagger} These authors contributed equally to this work.

Molecular and Cellular Biology, July 2008, p. 4620-4628, Vol. 28, No. 14
0270-7306/08/$08.00+0     doi:10.1128/MCB.02243-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gagne, J.-P., Isabelle, M., Lo, K. S., Bourassa, S., Hendzel, M. J., Dawson, V. L., Dawson, T. M., Poirier, G. G. (2008). Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes. Nucleic Acids Res 36: 6959-6976 [Abstract] [Full Text]  


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