Nuclear retention of ATM at sites of DNA double strand breaks.

The ATM protein kinase mediates a rapid induction of cellular responses to DNA double strand breaks (DSBs). ATM kinase activity is enhanced immediately after exposure of cells to DSB-inducing agents, but no changes in its amount or subcellular location following that activation have been reported. We speculated that some of the ATM molecules associate with sites of DSBs, while the rest of the nuclear ATM pool remains in the nucleoplasm, masking detection of the damage-associated ATM fraction. Using detergent extraction to remove nucleoplasmic proteins, we show here that immediately following induction of DSBs, a fraction of the ATM pool becomes resistant to extraction and is detected in nuclear aggregates. Colocalization of the retained ATM with the phosphorylated form of histone H2AX (gamma-H2AX) and with foci of the Nbs1 protein suggests that ATM associates with sites of DSBs. The striking correlation between the appearance of retained ATM and of gamma-H2AX, and the rapid association of a fraction of ATM with gamma-H2AX foci, are consistent with a major role for ATM in the early detection of DSBs and subsequent induction of cellular responses.

• Publication year

  2001

• Venue

  Journal of Biological Chemistry

• Publication date

  2001-10-12

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M102986200PMID 11454856
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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