Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells

Jong Soo Kim, Tatiana B. Krasieva, Hitoshi Kurumizaka, David J. Chen, A. Malcolm R Taylor, Kyoko Yokomori

    Research output: Contribution to journalArticle

    190 Citations (Scopus)

    Abstract

    Damage recognition by repair/checkpoint factors is the critical first step of the DNA damage response. DNA double strand breaks (DSBs) activate checkpoint signaling and are repaired by nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathways. However, in vivo kinetics of the individual factor responses and the mechanism of pathway choice are not well understood. We report cell cycle and time course analyses of checkpoint activation by ataxia-telangiectasia mutated and damage site recruitment of the repair factors in response to laserinduced DSBs. We found that MRN acts as a DNA damage marker, continuously localizing at unrepaired damage sites. Damage recognition by NHEJ factors precedes that of HR factors. HR factor recruitment is not influenced by NHEJ factor assembly and occurs throughout interphase. Damage site retention of NHEJ factors is transient, whereas HR factors persist at unrepaired lesions, revealing unique roles of the two pathways in mammalian cells.

    Original languageEnglish
    Pages (from-to)341-347
    Number of pages7
    JournalJournal of Cell Biology
    Volume170
    Issue number3
    DOIs
    Publication statusPublished - 2005 Sep 1

    ASJC Scopus subject areas

    • Cell Biology

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  • Cite this

    Kim, J. S., Krasieva, T. B., Kurumizaka, H., Chen, D. J., Taylor, A. M. R., & Yokomori, K. (2005). Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells. Journal of Cell Biology, 170(3), 341-347. https://doi.org/10.1083/jcb.200411083