Biology subjects

Batrin, R.

Publications and source records attributed to Batrin, R..

3 recordsLinked to original sources

bioRxiv2024

Smc5/6 association with microtubules controls dynamic pericentromeric chromatin folding

Centromeres and pericentromeres are specialized chromatin regions essential for accurate chromosome segregation. Smc5/6, which localizes at pericentromeres, can bind microtubules, yet its role in chromatin folding is unclear. Here, we investigate the functional relevance of Smc5/6- microtubule binding in yeast, by targeting two lysines (K624, K631) within the Smc5 hinge domain known to mediate this binding. Using high-temporal-resolution imaging, polymer modelling, and in vitro approaches with a separation-of-function mutant smc5-2KE, we demonstrate that microtubules binding by Smc5/6 constrains chromatin dynamics and promotes pericentromeric folding. The smc5-2KE mutant, combined with a hypomorphic kinetochore mutant (Mtw1-3xGFP), leads to spindle and cytokinesis defects and triggers the spindle checkpoint. Furthermore, homologous recombination repair in pericentromeres is compromised. Overall, our findings indicate that Smc5/6 - microtubules association safeguard pericentromeric architecture and genome stability during mitosis.

cell biology↗

bioRxiv2022

Global chromatin mobility induced by a DSB is dictated by chromosomal conformation and defines the outcome of Homologous Recombination.

Repair of DNA double-strand breaks (DSBs) is crucial for genome integrity. A conserved response to DSBs is an increase in chromatin mobility that can be local, at the site of the DSB, or global, at undamaged regions of the genome. Here we address the function of global chromatin mobility during homologous recombination (HR) of a single, targeted, controlled DSB. We set up a system that tracks HR in vivo over time and show that two types of DSB-induced global chromatin mobility are involved in HR, depending on the position of the DSB. In spatial proximal regions such as the pericentromeric region, a DSB therein induces global mobility that depends solely on H2A(X) phosphorylation and accelerates repair kinetics, but is not essential. In contrast, the global mobility induced by a DSB away from the centromere, becomes essential for HR repair and is triggered by homology search through a mechanism that depends on H2A(X) phosphorylation, checkpoint progression and Rad51. Our data demonstrate that global mobility is governed by chromosomal conformation and differentially coordinates repair by HR.

molecular biology↗

bioRxiv2020

Chromosome structure due to phospho-mimetic H2A modulates DDR through increased chromatin mobility

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.

genetics↗