RT Journal Article
SR Electronic
T1 Chromosome structure due to phospho-mimetic H2A modulates DDR through increased chromatin mobility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.25.397356
DO 10.1101/2020.11.25.397356
A1 Fernandez, Fabiola Garcia
A1 Lemos, Brenda
A1 Khalil, Yasmine
A1 Batrin, Renaud
A1 Haber, James E.
A1 Fabre, Emmanuelle
YR 2020
UL http://biorxiv.org/content/early/2020/11/26/2020.11.25.397356.abstract
AB In budding yeast and mammals, double strand breaks trigger global chromatin mobility together with the rapid phosphorylation of the histone H2A over an extensive region of the chromatin. To assess the role of H2A phosphorylation in this response to DNA damage, we have constructed strains where H2A has been mutated to the phospho-mimetic H2A-S129E. We show that H2A-S129E mutant increases global motion of chromosomes even in the absence of DNA damage. The intrinsic chromatin mobility of H2A-S129E is not due to checkpoint activation, histone degradation or kinetochore anchoring. Rather, the increased intra-chromosomal distances observed in H2A-S129E mutant are consistent with chromatin structural changes. In this context, the Rad953BP1-dependent-checkpoint becomes dispensable. The increase in chromatin dynamics is favorable to NHEJ of a single double-strand break but is accompanied by a sharp decrease in inter-chromosomal translocation rates. We propose that changes in chromosomal conformation due to H2A phosphorylation are sufficient to modulate the DDR and maintain genome integrity.Competing Interest StatementThe authors have declared no competing interest.