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 Scopus citations

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 (US)
Pages (from-to)341-347
Number of pages7
JournalJournal of Cell Biology
Volume170
Issue number3
DOIs
StatePublished - Sep 1 2005

ASJC Scopus subject areas

  • Cell Biology

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    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