Nuclear matrix binding site in the Rad51 recombinase

Mladenov, Emil; Kalev, Peter; Anachkova, Boyka

doi:10.1002/jcp.21665

Cited by 2 publications

(2 citation statements)

References 36 publications

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“…This region is important for binding of RAD51 to the nuclear matrix (Nagai et al, 2008;Mladenov et al, 2009). The nuclear matrix is a dynamic subnuclear compartment supporting the spatial organization of DNA metabolism (Anachkova et al, 2005;Zaidi et al, 2007;Courbet et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…This suggested that SIM is required for the accumulation of RAD51 at DNA damage. Although RAD51 is localized to both the nucleus and cytoplasm (Mladenov et al, 2009), the EGFP-tagged RAD51-AAAS and RAD51-V264K proteins showed cytoplasmic-dominant distributions, compared with RAD51-WT in GM0637 cells (supplementary material Fig. S4A).…”

Section: Rad51 Interacts With Sumo Through Its Sim Domainmentioning

confidence: 99%

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Activation of the SUMO modification system is required for the accumulation of RAD51 at sites containing DNA damage

Shima

Suzuki

Sun

et al. 2013

Journal of Cell Science

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SummaryGenetic information encoded in chromosomal DNA is challenged by intrinsic and exogenous sources of DNA damage. DNA doublestrand breaks (DSBs) are extremely dangerous DNA lesions. RAD51 plays a central role in homologous DSB repair, by facilitating the recombination of damaged DNA with intact DNA in eukaryotes. RAD51 accumulates at sites containing DNA damage to form nuclear foci. However, the mechanism of RAD51 accumulation at sites of DNA damage is still unclear. Post-translational modifications of proteins, such as phosphorylation, acetylation and ubiquitylation play a role in the regulation of protein localization and dynamics. Recently, the covalent binding of small ubiquitin-like modifier (SUMO) proteins to target proteins, termed SUMOylation, at sites containing DNA damage has been shown to play a role in the regulation of the DNA-damage response. Here, we show that the SUMOylation E2 ligase UBC9, and E3 ligases PIAS1 and PIAS4, are required for RAD51 accretion at sites containing DNA damage in human cells. Moreover, we identified a SUMO-interacting motif (SIM) in RAD51, which is necessary for accumulation of RAD51 at sites of DNA damage. These findings suggest that the SUMO-SIM system plays an important role in DNA repair, through the regulation of RAD51 dynamics.

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Section: Discussionmentioning

confidence: 99%

Section: Rad51 Interacts With Sumo Through Its Sim Domainmentioning

confidence: 99%

Activation of the SUMO modification system is required for the accumulation of RAD51 at sites containing DNA damage

Shima

Suzuki

Sun

et al. 2013

Journal of Cell Science

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Memoirs of an insult: sperm as a possible source of transgenerational epimutations and genetic instability

Boer¹,

Ramos²,

Vries³

et al. 2009

Molecular Human Reproduction

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Male transgenerational epigenetic effects have been discovered in the discipline of mouse radiation genetics, using genetic and non-genetic readouts. The mechanism to explain the origin of the transmission of epigenetic and genetic instability is still unknown. In a search for a hypothesis that could satisfy the data, we propose that regulation of chromosome structure in the germline, by the occupancy of matrix/scaffold associated regions, contains molecular memory function. The male germline is strikingly dynamic as to chromatin organization. This could explain why experience of irradiation stress leaves a persistent mark in the male germline only. To be installed, such memory requires both S-phase and chromatin reorganization during spermatogenesis and in the zygote, that likely also involves reorganization of loop domains. By this reorganization, another layer of information is added, needed to accommodate early embryonic development. Observations point at the involvement of DNA repair as inducer of transgenerational epigenetic modulation. Nuclear structure, chromatin composition and loop domain organization are aspects of human sperm variability that in many cases of assisted reproduction is increased due to inclusion of more incompletely differentiated/maturated sperm nuclei. Adjustment of loop domains in early embryo development can be anticipated and zygotic and cleavage stage S-phase repair activity will have to deal with potential paternal DNA lesions. Therefore, by changing male nucleus structure due to reproduction from impaired spermatogenesis, the transgenerational information content could be changed as well. We discuss aspects of male reproductive performance in the context of this hypothesis.

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Nuclear matrix binding site in the Rad51 recombinase

Cited by 2 publications

References 36 publications

Activation of the SUMO modification system is required for the accumulation of RAD51 at sites containing DNA damage

Activation of the SUMO modification system is required for the accumulation of RAD51 at sites containing DNA damage

Memoirs of an insult: sperm as a possible source of transgenerational epimutations and genetic instability

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