Abstract
Nonhomologous end-joining (NHEJ) is the predominant pathway that repairs DNA double-strand breaks (DSBs) in mammalian cells. The DNA-dependent protein kinase (DNA-PK), consisting of Ku and DNA-PK catalytic subunit (DNA-PKcs), is activated by DNA in vitro and is required for NHEJ. We report that DNA-PKcs is autophosphorylated at Thr2609 in vivo in a Ku-dependent manner in response to ionizing radiation. Phosphorylated DNA-PKcs colocalizes with both γ-H2AX and 53BP1 after DNA damage. Mutation of Thr2609 to Ala leads to radiation sensitivity and impaired DSB rejoining. These findings establish that Ku-dependent phosphorylation of DNA-PKcs at Thr2609 is required for the repair of DSBs by NHEJ.
Original language | English (US) |
---|---|
Pages (from-to) | 2333-2338 |
Number of pages | 6 |
Journal | Genes and Development |
Volume | 16 |
Issue number | 18 |
DOIs | |
State | Published - Sep 15 2002 |
Keywords
- Autophosphorytation
- DNA damage response
- DNA-PK
- DNA-PKcs
- Ionizing radiation
- Ku
- Nonhomologous end-joining
- Radiation sensitivity
ASJC Scopus subject areas
- Genetics
- Developmental Biology