Yeast ATM and ATR kinases use different mechanisms to spread histone H2A phosphorylation around a DNA double-strand break
Kevin Li, Gabriel Bronk, Jané Kondev, James E. Haber
Abstract
Significance Creation of a chromosomal double-strand break (DSB) is rapidly accompanied by extensive phosphorylation of yeast histone H2A isoform (H2AX in mammals) by Mec1 (ATR) and Tel1 (ATM) protein kinases. This phosphorylation, termed γ-H2AX, spreads 50 kb on either of the DSB, but how this phosphorylation is propagated is poorly understood. We have monitored the kinetics and extent of spreading individually for Mec1 and Tel1 and find that the patterns of spreading are significantly different for the two kinases. By comparing these experimental data to mathematical models of spreading, either by one-dimensional (1D) or 3D diffusion, we report that Bayesian model selections suggest Tel1 acts by directed motion along a chromatin fiber, whereas Mec1 primarily uses a 3D mode of propagation.