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Genetic Stabilization by p53 Involves Growth Regulatory and Repair Pathways.

Wiesmüller L - J. Biomed. Biotechnol. (2001)

Bottom Line: p53 performs a plethora of activities, which are directed towards the maintenance of the genomic integrity and constitute its universal role as a tumor suppressor. 1000 to 10000 latent p53 molecules are permanently available in order to monitor DNA exchange processes in mitotically growing cells.After the introduction of major DNA injuries the levels of posttranslationally modified p53 proteins rise, which in turn transcriptionally signal transient cell cycle arrest or apoptotic cell death, depending on the extent of damage.Taken together, p53 inhibits the manifestation of genomic instabilities at different control levels both during naturally occurring metabolic processes and in response to genotoxic treatments.

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ABSTRACT
p53 performs a plethora of activities, which are directed towards the maintenance of the genomic integrity and constitute its universal role as a tumor suppressor. 1000 to 10000 latent p53 molecules are permanently available in order to monitor DNA exchange processes in mitotically growing cells. After the introduction of major DNA injuries the levels of posttranslationally modified p53 proteins rise, which in turn transcriptionally signal transient cell cycle arrest or apoptotic cell death, depending on the extent of damage. Taken together, p53 inhibits the manifestation of genomic instabilities at different control levels both during naturally occurring metabolic processes and in response to genotoxic treatments.

No MeSH data available.


Related in: MedlinePlus

Maintenance of the genomic stability by multiplefunctions of p53. p53 surveils the genomic integrity via ahierarchy of different functions both during proliferation-associatedprocesses and during cellular stress situations.
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Figure 1: Maintenance of the genomic stability by multiplefunctions of p53. p53 surveils the genomic integrity via ahierarchy of different functions both during proliferation-associatedprocesses and during cellular stress situations.

Mentions: The critical question, whether the control of spontaneous andradiation-induced homologous recombination processes is tied top53's growth regulatory functions was answered unequivocally bythree groups [41, 42, 43]: Analyses of cell lines,expressing either different p53 mutants or wild-type p53 togetherwith the p53-antagonist HDM2, demonstrated that recombinationcontrol is performed independently of p53-functions intranscription and cell-cycle control. Furthermore, it wasobserved that small protein amounts are sufficient for theinhibition of recombination processes by p53, whereasgrowth-related functions are exerted in a dose-dependent manner.These findings support the dual role model (seeFigure 1), which attributes distinct functions to p53 inits latent and in its activated state, respectively [24]. Itis important to note that homologous recombination in mitoticallygrowing cells is suppressed by a factor of 1000 as compared tomeiotic recombination. This might explain why meiotic exchangerates are not further elevated by the loss of p53 functions[44]. On the other hand, elevated frequencies ofRad51-dependent recombination was observed to accompany cellularimmortalization processes [45]. Considering the experimentaldata, which describe the regulatory role of wild-type p53 in DNAexchange processes of mitotically growing cells [41, 42,43], the surveillance of homologous recombination by p53 is a goodcandidate to play a role in restraining spontaneous DNArearrangements. Consequently, p53 might prevent tumor formationboth by functions in growth regulatory and in repair processes.


Genetic Stabilization by p53 Involves Growth Regulatory and Repair Pathways.

Wiesmüller L - J. Biomed. Biotechnol. (2001)

Maintenance of the genomic stability by multiplefunctions of p53. p53 surveils the genomic integrity via ahierarchy of different functions both during proliferation-associatedprocesses and during cellular stress situations.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC79672&req=5

Figure 1: Maintenance of the genomic stability by multiplefunctions of p53. p53 surveils the genomic integrity via ahierarchy of different functions both during proliferation-associatedprocesses and during cellular stress situations.
Mentions: The critical question, whether the control of spontaneous andradiation-induced homologous recombination processes is tied top53's growth regulatory functions was answered unequivocally bythree groups [41, 42, 43]: Analyses of cell lines,expressing either different p53 mutants or wild-type p53 togetherwith the p53-antagonist HDM2, demonstrated that recombinationcontrol is performed independently of p53-functions intranscription and cell-cycle control. Furthermore, it wasobserved that small protein amounts are sufficient for theinhibition of recombination processes by p53, whereasgrowth-related functions are exerted in a dose-dependent manner.These findings support the dual role model (seeFigure 1), which attributes distinct functions to p53 inits latent and in its activated state, respectively [24]. Itis important to note that homologous recombination in mitoticallygrowing cells is suppressed by a factor of 1000 as compared tomeiotic recombination. This might explain why meiotic exchangerates are not further elevated by the loss of p53 functions[44]. On the other hand, elevated frequencies ofRad51-dependent recombination was observed to accompany cellularimmortalization processes [45]. Considering the experimentaldata, which describe the regulatory role of wild-type p53 in DNAexchange processes of mitotically growing cells [41, 42,43], the surveillance of homologous recombination by p53 is a goodcandidate to play a role in restraining spontaneous DNArearrangements. Consequently, p53 might prevent tumor formationboth by functions in growth regulatory and in repair processes.

Bottom Line: p53 performs a plethora of activities, which are directed towards the maintenance of the genomic integrity and constitute its universal role as a tumor suppressor. 1000 to 10000 latent p53 molecules are permanently available in order to monitor DNA exchange processes in mitotically growing cells.After the introduction of major DNA injuries the levels of posttranslationally modified p53 proteins rise, which in turn transcriptionally signal transient cell cycle arrest or apoptotic cell death, depending on the extent of damage.Taken together, p53 inhibits the manifestation of genomic instabilities at different control levels both during naturally occurring metabolic processes and in response to genotoxic treatments.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
p53 performs a plethora of activities, which are directed towards the maintenance of the genomic integrity and constitute its universal role as a tumor suppressor. 1000 to 10000 latent p53 molecules are permanently available in order to monitor DNA exchange processes in mitotically growing cells. After the introduction of major DNA injuries the levels of posttranslationally modified p53 proteins rise, which in turn transcriptionally signal transient cell cycle arrest or apoptotic cell death, depending on the extent of damage. Taken together, p53 inhibits the manifestation of genomic instabilities at different control levels both during naturally occurring metabolic processes and in response to genotoxic treatments.

No MeSH data available.


Related in: MedlinePlus