About: 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress

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About: 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress Goto Sponge NotDistinct Permalink

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Description	Completion of genome duplication is challenged by structural and topological barriers that impede progression of replication forks. Although this can seriously undermine genome integrity, the fate of DNA with unresolved replication intermediates is not known. Here, we show that mild replication stress increases the frequency of chromosomal lesions that are transmitted to daughter cells. Throughout G1, these lesions are sequestered in nuclear compartments marked by p53-binding protein 1 (53BP1) and other chromatin-associated genome caretakers. We show that the number of such 53BP1 nuclear bodies increases after genetic ablation of BLM, a DNA helicase associated with dissolution of entangled DNA. Conversely, 53BP1 nuclear bodies are partially suppressed by knocking down SMC2, a condensin subunit required for mechanical stability of mitotic chromosomes. Finally, we provide evidence that 53BP1 nuclear bodies shield chromosomal fragile sites sequestered in these compartments against erosion. Completion of genome duplication is challenged by structural and topological barriers that impede progression of replication forks. Although this can seriously undermine genome integrity, the fate of DNA with unresolved replication intermediates is not known. Here, we show that mild replication stress increases the frequency of chromosomal lesions that are transmitted to daughter cells. Throughout G1, these lesions are sequestered in nuclear compartments marked by p53-binding protein 1 (53BP1) and other chromatin-associated genome caretakers. We show that the number of such 53BP1 nuclear bodies increases after genetic ablation of BLM, a DNA helicase associated with dissolution of entangled DNA. Conversely, 53BP1 nuclear bodies are partially suppressed by knocking down SMC2, a condensin subunit required for mechanical stability of mitotic chromosomes. Finally, we provide evidence that 53BP1 nuclear bodies shield chromosomal fragile sites sequestered in these compartments against erosion. (en)
Title	53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress (en)
skos:prefLabel	53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress (en)
skos:notation	RIV/61989592:15110/11:10225038!RIV12-MSM-15110___
http://linked.open...avai/predkladatel	Lékařská fakulta
http://linked.open...avai/riv/aktivita	P
http://linked.open...avai/riv/aktivity	P(ED0030/01/01)
http://linked.open...iv/cisloPeriodika	3
http://linked.open...vai/riv/dodaniDat	2012
http://linked.open...aciTvurceVysledku	Bártek, Jiří
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Palackého v Olomouci / Lékařská fakulta
http://linked.open...dnocenehoVysledku	244225
http://linked.open...ai/riv/idVysledku	RIV/61989592:15110/11:10225038
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	REPAIR; CHECKPOINT; ATM; MITOSIS; ANAPHASE BRIDGES; GENOMIC INSTABILITY; FRAGILE SITES; DAMAGE RESPONSE; DOUBLE-STRAND BREAKS; ONCOGENE-INDUCED SENESCENCE (en)
http://linked.open.../riv/klicoveSlovo	REPAIR MITOSIS ANAPHASE BRIDGES CHECKPOINT DAMAGE RESPONSE FRAGILE SITES GENOMIC INSTABILITY ONCOGENE-INDUCED SENESCENCE ATM DOUBLE-STRAND BREAKS
http://linked.open...odStatuVydavatele	GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV	[D22637564B4F]
http://linked.open...i/riv/nazevZdroje	Nature Cell Biology (print)
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	11 (xsd:int)
http://linked.open...vavai/riv/projekt	Biomedicine for regional development and human resources
http://linked.open...UplatneniVysledku	2011
http://linked.open...v/svazekPeriodika	13
http://linked.open...iv/tvurceVysledku	Bártek, Jiří Lukáš, Jiří Bekker-Jensen, Simon Chan, Kok Lung Doil, Carsten Grofte, Merete Hickinson, Ian David Lukas, Claudia Neumann, Beate Pedersen, Ronni Solvhoj Savic, Velibor
issn	1465-7392
number of pages	12 (xsd:int)
http://localhost/t...ganizacniJednotka	15110
is http://linked.open...avai/riv/vysledek of	53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress

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