Chromatin mobility is increased at sites of DNA double-strand breaks

Krawczyk, Przemek M.; Borovski, Tijana; Stap, Jan; Cijsouw, Tony; Cate, Rosemarie ten; Medema, Jan Paul; Kanaar, Roland; Franken, Nicolaas A.P.; Aten, Jacob A.

doi:10.1242/jcs.089847

Cited by 135 publications

(162 citation statements)

References 31 publications

Supporting

Mentioning

147

Contrasting

Unclassified

Order By: Relevance

“…These observations are consistent with findings from studies of global chromatin movement using fluorescently tagged histones which showed that in mammalian cells, chromatin regions damaged by irradiation undergo no or only limited motion in the nucleus [37]. These results have recently been challenged by experiments indicating that DSBs roam a 2-to 3-fold larger nuclear area compared with undamaged chromatin [36]. As in the case of yeast, the mobility of the damaged regions in mammalian cells may depend on the type of lesion, as for example breaks induced by topoisomerase poisons show increased mobility compared with DSBs induced by irradiation [36,38].…”

Section: Insights From Long-term Time-lapse Imaging Of the Ddr In Sinsupporting

confidence: 89%

“…Live-cell imaging has recently emerged as a powerful technique for visualizing and quantifying the DNA repair process over time in single cells. This technique has been elegantly utilized for understanding the spatiotemporal aspects of the DDR such as the mobility of repair proteins [26,27] and their assembly into foci at damage sites [28][29][30], as well as the movements of damaged DNA and chromatin [31][32][33][34][35][36][37][38][39]. In the following sections, we describe these key areas in which live-cell imaging has provided unprecedented insights into the DDR and outline the main experimental techniques used for these analyses.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamics of the DNA damage response: insights from live-cell imaging

Karanam¹,

Loewer²,

Lahav³

2013

Briefings in Functional Genomics

View full text Add to dashboard Cite

All organisms have to safeguard the integrity of their genome to prevent malfunctioning and oncogenic transformation. Sophisticated DNA damage response mechanisms have evolved to detect and repair genomic lesions. With the emergence of live-cell microscopy of individual cells, we now begin to appreciate the complex spatiotemporal kinetics of the DNA damage response and can address the causes and consequences of the heterogeneity in the responses of genetically identical cells. Here, we highlight key discoveries where live-cell imaging has provided unprecedented insights into how cells respond to DNA double-strand breaks and discuss the main challenges and promises in using this technique.

show abstract

Section: Insights From Long-term Time-lapse Imaging Of the Ddr In Sinsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Dynamics of the DNA damage response: insights from live-cell imaging

Karanam¹,

Loewer²,

Lahav³

2013

Briefings in Functional Genomics

View full text Add to dashboard Cite

show abstract

“…This explains the increased effect for the tri-modality strategy. Our results can be further explained by a mechanism of interaction of two DNA double-strand breaks induced in close proximity by individual particles which yields chromosome aberrations (Franken et al 2011;Krawczyk et al 2012, Franken and. This mechanism of cell inactivation is suggested to dominate the responses at low doses up to 3 Gy and is most relevant in clinical radiotherapy with fraction doses in this range.…”

Section: Discussionmentioning

confidence: 62%

Analysis of enhancement at small and large radiation doses for effectiveness of inactivation in cultured cells by combining two agents with radiation

Franken

Kok

Crezee

et al. 2016

International Journal of Radiation Biology

View full text Add to dashboard Cite

Purpose: To evaluate the enhancement effect of two combined radiation-sensitizing agents in mammalian cells at small doses as compared to large doses using the linear-quadratic (LQ) mathematical model. Methods and materials: Data on clonogenic assays concerning the radio-enhancement effects of combined halogenated pyrimidines and hyperthermia or combined cisplatin and hyperthermia, as published in earlier reports, were analyzed according to the LQ-formula:). Effects of sensitizing agents on the linear parameter a and the quadratic parameter b are compared in order to evaluate differences depending on the applied dose, the possible relations to mechanisms of radiation sensitization and to derive suggestions for applications. Results: The values of the linear parameter a, which determines the effectiveness at low doses, are for all cell lines and all conditions more increased than the values of the parameter b which has a higher contribution at larger radiation doses. The combination of hyperthermia with halogenated pyrimidines to radiation as well as the combination of hyperthermia and cisplatin to radiation significantly increases the value of the linear parameter a, as compared to radiation alone or radiation combined with a single agent. Conclusions:The radiation enhancement factors of the values of linear and quadratic parameters demonstrate that the sensitizing agents have a larger effect on the linear parameter which is dominant at low radiation doses as is used in fractionated-radiation treatment in the clinic. Moreover, the effect is even further increased when two radiation sensitizers are used. ARTICLE HISTORY

show abstract

“…The single-cell resolution complements the analysis of genetic endpoints, such as survival or recombination rates and in vivo biochemical approaches, demonstrating that not only assembly but also disassembly of HR intermediates is critical (Symington and Heyer 2006). Tagging HR proteins and the DNA damage sites they act on revealed unanticipated dynamics not only of the damaged chromosome but also undamaged chromosomes in response to DSB formation (Dion et al 2012;Krawczyk et al 2012;MineHattab and Rothstein 2012). The mechanisms enabling this dynamics are not yet understood, and it is unclear how these processes relate to chromosomal territories (Fig.…”

Section: Regulation and Coordination With Nuclear Structure And Functionmentioning

confidence: 99%

Regulation of Recombination and Genomic Maintenance

Heyer

2015

Cold Spring Harb Perspect Biol

104

View full text Add to dashboard Cite

Recombination is a central process to stably maintain and transmit a genome through somatic cell divisions and to new generations. Hence, recombination needs to be coordinated with other events occurring on the DNA template, such as DNA replication, transcription, and the specialized chromosomal functions at centromeres and telomeres. Moreover, regulation with respect to the cell-cycle stage is required as much as spatiotemporal coordination within the nuclear volume. These regulatory mechanisms impinge on the DNA substrate through modifications of the chromatin and directly on recombination proteins through a myriad of posttranslational modifications (PTMs) and additional mechanisms. Although recombination is primarily appreciated to maintain genomic stability, the process also contributes to gross chromosomal arrangements and copy-number changes. Hence, the recombination process itself requires quality control to ensure high fidelity and avoid genomic instability. Evidently, recombination and its regulatory processes have significant impact on human disease, specifically cancer and, possibly, neurodegenerative diseases.

show abstract

Chromatin mobility is increased at sites of DNA double-strand breaks

Cited by 135 publications

References 31 publications

Dynamics of the DNA damage response: insights from live-cell imaging

Dynamics of the DNA damage response: insights from live-cell imaging

Analysis of enhancement at small and large radiation doses for effectiveness of inactivation in cultured cells by combining two agents with radiation

Regulation of Recombination and Genomic Maintenance

Contact Info

Product

Resources

About