DNA damage foci in mitosis are devoid of 53BP1

Nelson, Glyn; Buhmann, Matthias T.; Zglinicki, Thomas von

doi:10.4161/cc.8.20.9857

Cited by 87 publications

(85 citation statements)

References 25 publications

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“…1 Most of the IRIF in U87 and U251 cells were formed by 40 min following IR, which suggested the onset of G 2 /M checkpoint activation. In accord with previous reports, 35,36 the intensely stained 53BP1 appeared to be excluded from the chromatin. However, in irradiated miR-34a-overexpressing cells, 53BP1 foci and aggregates could be visible not only during telophase/cytokinesis, 38 but also in prophase.…”

Section: Mir-34a Disturbs Mitotic Progression In Irradiated Cellssupporting

confidence: 80%

“…34 During mitosis, 53BP1 and a number of γH2AX-dependent factors fail to localize on the condensed chromosomes and to form IRIF. 35,36 The aberrant mitotic progression results in accumulation of de novo DNA damage, which can be propagated to the next cell cycle but usually initiates permanent cell cycle arrest and cell death. 34,37 To explore the impact of miR-34a on mitosis, we examined microscopically asynchronous cells subjected to the low IR doses (1.3 Gy and 1 Gy for U87 and U251 cell lines, respectively) and related mitotic phases to the presence of 53BP1 IRIF.…”

Section: Mir-34a Disturbs Mitotic Progression In Irradiated Cellsmentioning

confidence: 99%

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microRNA-34a promotes DNA damage and mitotic catastrophe

et al. 2013

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Section: Mir-34a Disturbs Mitotic Progression In Irradiated Cellssupporting

confidence: 80%

Section: Mir-34a Disturbs Mitotic Progression In Irradiated Cellsmentioning

confidence: 99%

microRNA-34a promotes DNA damage and mitotic catastrophe

et al. 2013

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“…19 In contrast, 53BP1 is not recruited to DNA lesions during mitosis until cells progress to the following G1 phase. 19,22,23 Here we show that 53BP1 is phosphorylated in its C-terminal domain by Plk1 and Cdk1 during mitosis and that this modification supresses the ability of 53BP1 to bind to ubiquitinated histones and to localize to DNA damage foci. We propose a model by which the suppression of 53BP1 function is strictly limited to mitosis.…”

Section: Introductionmentioning

confidence: 98%

Polo-like kinase 1 inhibits DNA damage response during mitosis

et al. 2015

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Abbreviations: 53BP1, p53 binding protein 1; ATM, ataxia telangiectasia mutated kinase; BRCA1, breast cancer type 1 susceptibility protein; Cdk, cyclin dependent kinase; DDR, DNA damage response; Plk1, Polo-like kinase 1; H2AX, histone variant H2AX; IR -ionizing radiation; MDC1, mediator of DNA damage checkpoint protein 1; NCS -neocarzinostatin; NZ -nocodazole; PTIP, PAX transactivation activation domain-interacting protein; RIF1, Rap1-interacting factor 1 homolog; RNAi, RNA interference; RNF8, RING finger protein 8; RNF168, RING finger protein 168.In response to genotoxic stress, cells protect their genome integrity by activation of a conserved DNA damage response (DDR) pathway that coordinates DNA repair and progression through the cell cycle. Extensive modification of the chromatin flanking the DNA lesion by ATM kinase and RNF8/RNF168 ubiquitin ligases enables recruitment of various repair factors. Among them BRCA1 and 53BP1 are required for homologous recombination and nonhomologous end joining, respectively. Whereas mechanisms of DDR are relatively well understood in interphase cells, comparatively less is known about organization of DDR during mitosis. Although ATM can be activated in mitotic cells, 53BP1 is not recruited to the chromatin until cells exit mitosis. Here we report mitotic phosphorylation of 53BP1 by Plk1 and Cdk1 that impairs the ability of 53BP1 to bind the ubiquitinated H2A and to properly localize to the sites of DNA damage. Phosphorylation of 53BP1 at S1618 occurs at kinetochores and in cytosol and is restricted to mitotic cells. Interaction between 53BP1 and Plk1 depends on the activity of Cdk1. We propose that activity of Cdk1 and Plk1 allows spatiotemporally controlled suppression of 53BP1 function during mitosis.

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“…4B). While the molecular basis of this DDR abrogation is still elusive, it appears to operate at the level of ubiquitylating enzymes that control 53BP1 and BRCA1 focus formation (Nelson et al 2009;Giunta et al 2010;Nakamura et al 2010;van Vugt et al 2010). It is speculated that early DNA damage signaling takes place in mitosis as a priming event for full DDR activation in the following G1 phase (Giunta et al 2010).…”

Section: Temporal Organization Of Ddr Focimentioning

confidence: 99%

Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications

Polo¹,

Jackson²

2011

Genes Dev.

979

946

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Genome integrity is constantly monitored by sophisticated cellular networks, collectively termed the DNA damage response (DDR). A common feature of DDR proteins is their mobilization in response to genotoxic stress. Here, we outline how the development of various complementary methodologies has provided valuable insights into the spatiotemporal dynamics of DDR protein assembly/disassembly at sites of DNA strand breaks in eukaryotic cells. Considerable advances have also been made in understanding the underlying molecular mechanisms for these events, with post-translational modifications of DDR factors being shown to play prominent roles in controlling the formation of foci in response to DNA-damaging agents. We review these regulatory mechanisms and discuss their biological significance to the DDR.

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DNA damage foci in mitosis are devoid of 53BP1

Cited by 87 publications

References 25 publications

microRNA-34a promotes DNA damage and mitotic catastrophe

microRNA-34a promotes DNA damage and mitotic catastrophe

Polo-like kinase 1 inhibits DNA damage response during mitosis

Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications

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