APLF (C2orf13) is a novel component of poly(ADP-ribose) signaling in mammalian cells

Rulten, Stuart L, Cortes-Ledesma, Felipe, Guo, Liandi, Iles, Natasha J and Caldecott, Keith W (2008) APLF (C2orf13) is a novel component of poly(ADP-ribose) signaling in mammalian cells. Molecular and Cellular Biology, 28 (14). pp. 4620-4628. ISSN 0270-7306

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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 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Stuart Rulten
Date Deposited: 06 Feb 2012 19:03
Last Modified: 13 Mar 2017 23:45
URI: http://sro.sussex.ac.uk/id/eprint/19206

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