Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1

Dragana Ahel, Zuzana Horejsi, Nicola Wiechens, Sophie E. Polo, Elisa Garcia-Wilson, Ivan Ahel, Helen Flynn, Mark Skehel, Stephen C. West, Stephen P. Jackson, Tom Owen-Hughes, Simon J. Boulton

    Research output: Contribution to journalArticle

    352 Citations (Scopus)

    Abstract

    Posttranslational modifications play key roles in regulating chromatin plasticity. Although various chromatin-remodeling enzymes have been described that respond to specific histone modifications, little is known about the role of poly[adenosine 5'-diphosphate (ADP)-ribose] in chromatin remodeling. Here, we identify a chromatin-remodeling enzyme, ALC1 (Amplified in Liver Cancer 1, also known as CHD1L), that interacts with poly(ADP-ribose) and catalyzes PARP1-stimulated nucleosome sliding. Our results define ALC1 as a DNA damage-response protein whose role in this process is sustained by its association with known DNA repair factors and its rapid poly(ADP-ribose)-dependent recruitment to DNA damage sites. Furthermore, we show that depletion or overexpression of ALC1 results in sensitivity to DNA-damaging agents. Collectively, these results provide new insights into the mechanisms by which poly(ADP-ribose) regulates DNA repair.

    Original languageEnglish
    Pages (from-to)1240-1243
    Number of pages4
    JournalScience
    Volume325
    Issue number5945
    DOIs
    Publication statusPublished - 4 Sep 2009

    Keywords

    • DAMAGE
    • POLY(ADP-RIBOSYL)ATION
    • BINDING
    • POLYNUCLEOSOMES
    • IDENTIFICATION
    • RELAXATION
    • PROTEINS
    • MOTIFS

    Cite this

    Ahel, D., Horejsi, Z., Wiechens, N., Polo, S. E., Garcia-Wilson, E., Ahel, I., Flynn, H., Skehel, M., West, S. C., Jackson, S. P., Owen-Hughes, T., & Boulton, S. J. (2009). Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1. Science, 325(5945), 1240-1243. https://doi.org/10.1126/science.1177321