Ddc1p is a member of the DNA damage checkpoint, a conserved surveillance mechanism whose main function is to delay cell cycle progression in the presence of damaged chromosomes, allowing time for DNA repair. Ddc1p is phosphorylated periodically during a normal cell cycle and becomes hyperphosphorylated in response to DNA damage, but nothing is currently known about the functional meaning of this modification. By mutating Ddc1 s putative phosphorylation sites, we have identified a role for the post-traductional modification in checkpoint inactivation in response to DNA double strand brakes: the mutant strain, in fact, is able to adapt to irreparable DSB earlier than the wild type, and this effect is increased when the protein is overexpressed. Moreover, even the overexpression of wild type Ddc1p induces a faster adaptation; a possible explanation is that Ddc1p overexpression regulates the rate of DNA resection at the lesion, which is strictly correlated with the processes of checkpoint activation and inactivation.
La proteina di checkpoint Ddc1 svolge un ruolo nel processo di adattamento ai danni al DNA / L.l. Di Nola ; Tutor: M. Muzi Falconi ; coordinatore: P. Plevani. DIPARTIMENTO DI SCIENZE BIOMOLECOLARI E BIOTECNOLOGIE, 2005. 18. ciclo, Anno Accademico 2004/2005.
La proteina di checkpoint Ddc1 svolge un ruolo nel processo di adattamento ai danni al DNA
L.L. DI NOLA
2005
Abstract
Ddc1p is a member of the DNA damage checkpoint, a conserved surveillance mechanism whose main function is to delay cell cycle progression in the presence of damaged chromosomes, allowing time for DNA repair. Ddc1p is phosphorylated periodically during a normal cell cycle and becomes hyperphosphorylated in response to DNA damage, but nothing is currently known about the functional meaning of this modification. By mutating Ddc1 s putative phosphorylation sites, we have identified a role for the post-traductional modification in checkpoint inactivation in response to DNA double strand brakes: the mutant strain, in fact, is able to adapt to irreparable DSB earlier than the wild type, and this effect is increased when the protein is overexpressed. Moreover, even the overexpression of wild type Ddc1p induces a faster adaptation; a possible explanation is that Ddc1p overexpression regulates the rate of DNA resection at the lesion, which is strictly correlated with the processes of checkpoint activation and inactivation.Pubblicazioni consigliate
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