H2AX and MDC1 but not ATM mediate telomere fusions in DNA-PKcs-inhibited cells.

<p>(<b>A</b>) MEFs deficient for ATM and wt controls were treated with NU7026 for 24 hours and the number of fusions per metaphase quantified by telomere FISH. (<b>B</b>) Wild-type MEFs were treated with either NU7026, ATM inhibitor KU55933, or both for 24 hours and telomere fusions were quantified by telomere FISH on metaphase spreads. (<b>C</b>) MEFs deficient for both 53BP1 and ATM (<i>Trp53bp1</i>^−/−/<i>Atm</i>^−/−) were treated with NU7026 and metaphases analyzed for telomere fusions. (<b>D</b>) Schematic of the genetic requirements for DNA-PKcs-inhibited telomeres. H2AX and MDC1 but not ATM normally promote replication-dependent telomere fusions. In cells proficient for 53BP1, fusions are mediated via ligase IV (“high efficiency” C-NHEJ). In the absence of 53BP1, a PARP1-dependent pathway mediates residual fusions (“low efficiency” A-NHEJ).