Localization of Cyclin A at the Sites of Cellular DNA Replication

Sobczak-Thépot, Joëlle; Harper, Francis; Florentin, Y.; Zindy, Frédérique; Bréchot, Christian; Puvion, Edmond

doi:10.1006/excr.1993.1118

Cited by 108 publications

(63 citation statements)

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“…2 B shows three representative cardiomyocytes immunoreactive for cyclin A. Also, cyclin A immunostaining was localized to the nuclear region of cardiomyocytes, consistent with previous reports that cyclin A and Cdk2 localize to nuclei of other cell types, particularly at sites of DNA replication (43,44). Because desmin localizes to the Z bands of fetal and adult cardiomyocytes (45) it makes a good marker for them.…”

Section: Resultssupporting

confidence: 87%

Disappearance of cyclin A correlates with permanent withdrawal of cardiomyocytes from the cell cycle in human and rat hearts.

et al. 1995

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The regulated expression of cyclins controls the cell cycle. Because cardiomyocytes in adult mammals withdraw permanently from the cell cycle and thus cannot regenerate after injury, we examined cyclin expression during development by comparing cyclin A-E mRNA levels in fetal and adult human hearts. Cyclin B mRNA was detectable in adult hearts, although at a level markedly lower than that in fetal hearts. Levels of cyclin C, D1, D2, D3, and E mRNA were essentially identical in the two groups. In contrast, cyclin A mRNA was undetectable in adult hearts whereas cyclin A mRNA and protein were readily detectable in fetal hearts and cardiomyocytes, respectively. We then measured cyclin A mRNA and protein levels in rat hearts at four stages of development (fetal and 2, 14, and 28 d). Cyclin A mRNA and protein levels decreased quickly after birth (to 37% at day 2) and became undetectable within 14 d, an observation consistent with reports that cardiomyocytes stop replicating in rats by the second to third postnatal week. This disappearance of cyclin A gene expression in human and rat hearts at the time cardiomyocytes become terminally differentiated suggests that cyclin A downregulation is important in the permanent withdrawal of cardiomyocytes from the cell cycle. (J. Clin. Invest. 1995. 95:2275-2280

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Section: Resultssupporting

confidence: 87%

Disappearance of cyclin A correlates with permanent withdrawal of cardiomyocytes from the cell cycle in human and rat hearts.

et al. 1995

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“…ase ␦ cofactor whose distribution in S phase closely follows that of active RF (Bravo and Macdonald-Bravo;1987;Sobczak-Thépot et al, 1993). By using EM, we found that clumps of PCNA labeling were associated with some BCL6 bodies in a manner very similar to that observed upon a short pulse of any XdU ( Fig.…”

Section: Pcna-visualized Rf Associatedsupporting

confidence: 61%

The relationship between BCL6 bodies and nuclear sites of normal and halogenated DNA and RNA synthesis

Puvion‐Dutilleul¹,

Souquere-Besse²,

Albagli-Curiel

2003

Microscopy Res & Technique

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BCL6 is a POZ/BTB and zinc finger transcription factor that self-interacts and accumulates into discrete nuclear "bodies" of unknown function. We recently reported that BCL6 bodies associate with bromodeoxyuridine (BrdU)-substituted DNA, suggesting their implication in replication. To examine this possibility, we examine here by electron and confocal microscopy the relation between BCL6 bodies and replication foci (RF) using incorporation of various halogenated nucleotides (BrdU, chlorodeoxyuridine, CldU, and iododeoxyuridine, IdU) or PCNA (proliferating cell nuclear antigen) staining. We show that BCL6 bodies are found associated with RF, as revealed by PCNA staining. However, such association is markedly prolonged upon BrdU or CldU incorporation, but less, or not at all, upon IdU incorporation. Pulse-chase and double-labeling experiments indicate that IdU-substituted DNA leaves BCL6 bodies after a few tenths of minutes while BrdUor CldU-substituted DNA stalls in their vicinity for several hours, thereby giving the characteristic "crowns" of DNA entirely surrounding BCL6 bodies. In all cases, however, the halogenated DNA ends up undergoing a movement from BCL6 bodies toward nucleoplasm and nuclear periphery to reach euchromatin and heterochromatin, respectively. We propose that replicating DNA is prone to be bound by BCL6, while BrdU/CldU incorporation increases this propensity possibly because these two events have synergistic effects on the structure and chromatinisation of the newly synthesized DNA. Finally, despite the known proximity between nuclear sites of transcription and replication, we show via several approaches that BCL6 bodies do not appear to be involved either in RNA synthesis or storage.

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“…It is predominantly nuclear (Bailly et al, 1992;Dulić et al, 1998;Pagano et al, 1992;Pines and Hunter, 1991) and shuttles between the nucleus and cytoplasm (Jackman et al, 2002). Cyclin A2 distribution is diffuse during mitosis and interphase, apart from dots corresponding to replication foci (Cardoso et al, 1993;Sobczak-Thepot et al, 1993) and centrosomes (Bailly et al, 1992;Pascreau et al, 2010). A priori, neither of these corresponds to the foci that we observed.…”

Section: Results and Discussion Cyclin A2 Ubiquitylation Occurs Predomentioning

confidence: 72%

High resolution live cell imaging reveals novel cyclin A2 degradation foci involving autophagy

Loukil

Zonca

Rebouissou

et al. 2014

Journal of Cell Science

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Cyclin A2 is a key player in the regulation of the cell cycle. Its degradation in mid-mitosis relies on the ubiquitin-proteasome system (UPS). Using high-resolution microscopic imaging, we find that cyclin A2 persists beyond metaphase. Indeed, we identify a novel cyclin-A2-containing compartment that forms dynamic foci. Fö rster (or fluorescence) resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM) analyses show that cyclin A2 ubiquitylation takes place predominantly in these foci before spreading throughout the cell. Moreover, inhibition of autophagy in proliferating cells induces the stabilisation of a subset of cyclin A2, whereas induction of autophagy accelerates the degradation of cyclin A2, thus showing that autophagy is a novel regulator of cyclin A2 degradation.

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Localization of Cyclin A at the Sites of Cellular DNA Replication

Cited by 108 publications

References 0 publications

Disappearance of cyclin A correlates with permanent withdrawal of cardiomyocytes from the cell cycle in human and rat hearts.

Disappearance of cyclin A correlates with permanent withdrawal of cardiomyocytes from the cell cycle in human and rat hearts.

The relationship between BCL6 bodies and nuclear sites of normal and halogenated DNA and RNA synthesis

High resolution live cell imaging reveals novel cyclin A2 degradation foci involving autophagy

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