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Mol. Cell. Biol. doi:10.1128/MCB.02243-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

APLF (C2orf13) is a Novel Component of Poly (ADP-ribose) Signalling in Mammalian Cells

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

^* To whom correspondence should be addressed. Email: k.w.caldecott{at}sussex.ac.uk.

	Abstract

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 post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. Protein poly ADP-ribosylation 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-ribosylation in vitro, and this activity is dependant on its capacity to bind the polymer. In addition, transient over-expression 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) signalling in mammalian cells.