Interphase Chromatin Dynamics in Response to Local DNA Damage

In mammals, there is a complex and intriguing relationship between DNA repair and gametogenesis. DNA repair mechanisms are involved not only in the repair of different types of DNA damage in developing germline cells, but also take part in the meiotic recombination process. Furthermore, the DNA repair mechanisms should tolerate mutations occurring during gametogenesis, to a limited extent. In the present review, several gametogenic aspects of DNA mismatch repair, homologous recombination repair and postreplication repair are discussed. In addition, the role of DNA damage-induced cell cycle checkpoint control is considered briefly. It appears that many genes encoding proteins that take part in DNA repair mechanisms show enhanced or specialized expression during mammalian gametogenesis, and several gene knockout mouse models show male or female infertility. On the basis of such knowledge and models, future experiments may provide more information about the precise relationship between DNA repair, chromatin dynamics, and genomic stability versus instability during gametogenesis.

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Quantification of Interphase Chromatin Dynamics in Fission Yeast

Biophysical Journal ◽

10.1016/j.bpj.2014.11.2952 ◽

2015 ◽

Vol 108 (2) ◽

pp. 538a

Author(s):

Takeshi Sugawara ◽

Kenta Masuda ◽

Jun-ichi Uewaki ◽

Akinori Awazu ◽

Hiraku Nishimori ◽

...

Keyword(s):

Fission Yeast ◽

Interphase Chromatin ◽

Chromatin Dynamics

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Imaging DNA damage-dependent chromatin dynamics via nonlinear photoperturbation

CLEO: 2013 ◽

10.1364/cleo_si.2013.ctu2m.6 ◽

2013 ◽

Author(s):

M. Tomas ◽

P. Blumhardt ◽

A. Deutzmann ◽

D. Kromm ◽

A. Leitenstorfer ◽

...

Keyword(s):

Dna Damage ◽

Chromatin Dynamics

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Monoubiquitylation of histone H2B contributes to the bypass of DNA damage during and after DNA replication

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1612633114 ◽

2017 ◽

Vol 114 (11) ◽

pp. E2205-E2214 ◽

Cited By ~ 19

Author(s):

Shih-Hsun Hung ◽

Ronald P. Wong ◽

Helle D. Ulrich ◽

Cheng-Fu Kao

Keyword(s):

Dna Damage ◽

Replication Fork ◽

Dna Lesions ◽

Template Switching ◽

Lesion Bypass ◽

Dna Damage Tolerance ◽

Cytological Evidence ◽

Histone H2b ◽

Chromatin Dynamics ◽

Dna Lesion

DNA lesion bypass is mediated by DNA damage tolerance (DDT) pathways and homologous recombination (HR). The DDT pathways, which involve translesion synthesis and template switching (TS), are activated by the ubiquitylation (ub) of PCNA through components of the RAD6-RAD18 pathway, whereas the HR pathway is independent of RAD18. However, it is unclear how these processes are coordinated within the context of chromatin. Here we show that Bre1, an ubiquitin ligase specific for histone H2B, is recruited to chromatin in a manner coupled to replication of damaged DNA. In the absence of Bre1 or H2Bub, cells exhibit accumulation of unrepaired DNA lesions. Consequently, the damaged forks become unstable and resistant to repair. We provide physical, genetic, and cytological evidence that H2Bub contributes toward both Rad18-dependent TS and replication fork repair by HR. Using an inducible system of DNA damage bypass, we further show that H2Bub is required for the regulation of DDT after genome duplication. We propose that Bre1-H2Bub facilitates fork recovery and gap-filling repair by controlling chromatin dynamics in response to replicative DNA damage.

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Micron-scale coherence in interphase chromatin dynamics

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1220313110 ◽

2013 ◽

Vol 110 (39) ◽

pp. 15555-15560 ◽

Cited By ~ 124

Author(s):

A. Zidovska ◽

D. A. Weitz ◽

T. J. Mitchison

Keyword(s):

Interphase Chromatin ◽

Chromatin Dynamics

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Multi-scale tracking reveals scale-dependent chromatin dynamics after DNA damage

Molecular Biology of the Cell ◽

10.1091/mbc.e17-05-0317 ◽

2017 ◽

Vol 28 (23) ◽

pp. 3323-3332 ◽

Cited By ~ 33

Author(s):

Judith Miné-Hattab ◽

Vincent Recamier ◽

Ignacio Izeddin ◽

Rodney Rothstein ◽

Xavier Darzacq

Keyword(s):

Dna Damage ◽

Time Scales ◽

Persistence Length ◽

Chromatin Dynamics ◽

Strand Breaks ◽

Multi Scale ◽

Repair Protein ◽

Global Increase ◽

Dna Motion ◽

Short Time

The dynamic organization of genes inside the nucleus is an important determinant for their function. Using fast DNA tracking microscopy in Saccharomyces cerevisiae cells and improved analysis of mean-squared displacements, we quantified DNA motion at time scales ranging from 10 ms to minutes and found that following DNA damage, DNA exhibits distinct subdiffusive regimes. In response to double-strand breaks, chromatin is more mobile at large time scales, but, surprisingly, its mobility is reduced at short time scales. This effect is even more pronounced at the site of damage. Such a pattern of dynamics is consistent with a global increase in chromatin persistence length in response to DNA damage. Scale-dependent nuclear exploration is regulated by the Rad51 repair protein, both at the break and throughout of the genome. We propose a model in which stiffening of the damaged ends by the repair complex, combined with global increased stiffness, act like a “needle in a ball of yarn,” enhancing the ability of the break to traverse the chromatin meshwork.

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