Diffusion of activated ATM explains γH2AX and MDC1 spread beyond the DNA damage site.

ABSTRACT: During DNA repair, ATM-induced H2AX histone phosphorylation and MDC1 recruitment spread megabases beyond the damage site. While loop extrusion has been suggested to drive this spread, the underlying mechanism remains unclear. Herein, we provide two lines of evidence that loop extrusion is not the only driver of damage-induced γH2AX spread. First, cohesin loader NIPBL and cohesin subunit RAD21 accumulate considerably later than the phosphorylation of H2AX and MDC1 recruitment at micro-IR-induced damage. Second, auxin-induced RAD21 depletion does not affect γH2AX/MDC1 spread following micro-irradiation or DSB induction by zeocin. To determine if diffusion of activated ATM could account for the observed behavior, we measured the exchange rate and diffusion constants of ATM and MDC1 within dam

SUBMITTER: Danovski G 

PROVIDER: S-EPMC11416226 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature