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

Rulten, Stuart, Cortes-Ledesma, Felipe, Guo, Liandi, Iles, Natasha and Caldecott, Keith (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(ADPribosyl) 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
Subjects: Q Science > QP Physiology
Depositing User: Stuart Rulten
Date Deposited: 17 Jul 2008
Last Modified: 10 Mar 2017 05:16
URI: http://sro.sussex.ac.uk/id/eprint/1795
Google Scholar:14 Citations

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