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

journal contribution
posted on 2023-06-07, 21:57 authored by Stuart L Rulten, Felipe Cortes-Ledesma, Liandi Guo, Natasha J Iles, Keith CaldecottKeith Caldecott
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Molecular and Cellular Biology

ISSN

0270-7306

Publisher

American Society for Microbiology

Issue

14

Volume

28

Page range

4620-4628

Pages

9.0

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

First Open Access (FOA) Date

2016-03-22

First Compliant Deposit (FCD) Date

2016-11-10

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