Checkpoint kinases and the INO80 nucleosome remodeling complex enhance global chromatin mobility in response to DNA damage

Seeber, Andrew; Dion, Vincent; Gasser, Susan M.

doi:10.1101/gad.222992.113

Cited by 117 publications

(164 citation statements)

References 37 publications

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“…The change in mobility of the broken locus is termed "local" or "cis." Interestingly, in budding yeast, unbroken chromosomes also increase the volume that they explore after DNA damage, termed "global" or "trans" (Mine-Hattab and Rothstein 2012;Seeber et al 2013). The increase in both global and local mobility in haploid and diploid budding yeast cells is genetically controlled.…”

Section: Dsb Dynamicsmentioning

confidence: 99%

“…For example, both depend on the Rad51 recombinase (Dion et al 2012;Mine-Hattab and Rothstein 2012). In haploid budding yeast, the increase in local mobility depends on Rad54 as well as two checkpoint proteins, Rad9 and Mec1 (Dion et al 2012;Seeber et al 2013). In diploid cells, deletion of SAE2, which likely causes a delayed appearance of ssDNA, also delays the increase in local chromosome mobility (Mine-Hattab and Rothstein 2012).…”

Section: Dsb Dynamicsmentioning

confidence: 99%

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Cell Biology of Mitotic Recombination

Lisby

Rothstein

2015

Cold Spring Harb Perspect Biol

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Homologous recombination provides high-fidelity DNA repair throughout all domains of life. Live cell fluorescence microscopy offers the opportunity to image individual recombination events in real time providing insight into the in vivo biochemistry of the involved proteins and DNA molecules as well as the cellular organization of the process of homologous recombination. Herein we review the cell biological aspects of mitotic homologous recombination with a focus on Saccharomyces cerevisiae and mammalian cells, but will also draw on findings from other experimental systems. Key topics of this review include the stoichiometry and dynamics of recombination complexes in vivo, the choreography of assembly and disassembly of recombination proteins at sites of DNA damage, the mobilization of damaged DNA during homology search, and the functional compartmentalization of the nucleus with respect to capacity of homologous recombination.

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Section: Dsb Dynamicsmentioning

confidence: 99%

Section: Dsb Dynamicsmentioning

confidence: 99%

Cell Biology of Mitotic Recombination

Lisby

Rothstein

2015

Cold Spring Harb Perspect Biol

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“…Interestingly, the concerted activity of the DDR and remodelers is not restricted to the site of DNA damage. Checkpoint activation, even in the absence of damage, leads to a more generalized increase in chromatin mobility that was dependent on Mec1 and its downstream target kinase Rad53 [36,43] (Fig. 1).…”

Section: The Mobility Of Dna Dsbsmentioning

confidence: 96%

“…Recent results implicate two nucleosome remodelers (INO80-C and SWR-C) in regulating this chromatin mobility and in the association of DNA damage with perinuclear sites [30,[35][36][37]. It is thus relevant to review chromatin dynamics in terms of local nucleosome composition, chromatin compaction and the precise position of the locus within the nuclear sphere.…”

Section: Introductionmentioning

confidence: 97%

INO80-C and SWR-C: Guardians of the Genome

Gerhold

Hauer

Gasser

2015

Journal of Molecular Biology

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“…We now explore the consequences of chromatin reorganization after DSB induction, where the dynamics of a chromatin locus in the proximity of the break is modified [19]. The changes are revealed by the subdiffusion behavior.…”

Section: Following Polymer Decompaction the Local Search Time Decmentioning

confidence: 99%

Encounter times of chromatin loci influenced by polymer decondensation

Amitai

Holcman

2018

Phys. Rev. E

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The time for a DNA sequence to find its homologous counterpart depends on a long random search inside the cell nucleus. Using polymer models, we compute here the mean first encounter time (MFET) between two sites located on two different polymer chains and confined locally by potential wells. We find that reducing tethering forces acting on the polymers results in local decondensation, and numerical simulations of the polymer model show that these changes are associated with a reduction of the MFET by several orders of magnitude. We derive here new asymptotic formula for the MFET, confirmed by Brownian simulations. We conclude from the present modeling approach that the fast search for homology is mediated by a local chromatin decondensation due to the release of multiple chromatin tethering forces. The present scenario could explain how the homologous recombination pathway for double-stranded DNA repair is controlled by its random search step. DOI: 10.1103/PhysRevE.97.032417 Repairing DNA double-strand breaks (DSBs) is a key step for cell survival. However, the underlying physical mechanism remains difficult to describe, mostly because it involves multiple molecular steps involving small (nanometer) and large (micrometer) scales. During the homologous recombination (HR) pathway, broken strands perform inside a large portion of the cell nucleus a random search for a homologous DNA template. Once this template is found, it will be used to copy the missing base pairs before repair [1]. As revealed by single-particle trajectories of chromatin [2,3], following a DSB, the broken locus dynamics is modified so that it can scan a larger area of the nucleus. This modification was attributed in part to chromatin decondensation and the release of tethering forces acting locally on the chromatin [4]. These changes could have consequences on the search for a homologous template. We present here polymer modeling and analytical tools to further characterize this search step.We recall that search processes involving two loci located on the same polymers have been investigated in the context of polymer looping [5][6][7][8]. However, much less is known about the mean time for two monomers belonging to two different polymers. The multiple relaxation times associated with the polymer dynamics [9] shows that computing the looping time cannot be obtained by the classical activation escape from a potential well (representing the end-to-end distance energy) [10]. For a long polymer, the mean encounter time is influenced by the slowest internal relaxation times of the polymer [9]. However, it is not clear how these times contribute to the mean encounter time for two monomers located on two different polymers. In addition, in a confined environment, the probability distribution function of monomers varies along the polymer chain [11,12], which again can influence the search time.To account for chromatin reorganization following DSB [4], we study here the random search of two monomers that belongs to two different monomers using the Ro...

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Checkpoint kinases and the INO80 nucleosome remodeling complex enhance global chromatin mobility in response to DNA damage

Cited by 117 publications

References 37 publications

Cell Biology of Mitotic Recombination

Cell Biology of Mitotic Recombination

INO80-C and SWR-C: Guardians of the Genome

Encounter times of chromatin loci influenced by polymer decondensation

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