التفاصيل البيبلوغرافية
| العنوان: |
PCNA ubiquitylation as the wet readout of a Post-Replication Repair computational model |
| المؤلفون: |
F. Amara, D. Besozzi, M. Muzi-Falconi, P. Plevani, R. Colombo, F. Spadaro |
| المساهمون: |
F. Amara, R. Colombo, F. Spadaro, D. Besozzi, M. Muzi-Falconi, P. Plevani |
| سنة النشر: |
2011 |
| المجموعة: |
The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: |
Settore BIO/11 - Biologia Molecolare, Settore INF/01 - Informatica, Settore BIO/10 - Biochimica |
| الوصف: |
To maintain genome stability, cells have developed repair and tolerance mechanisms to counteract the effects of DNA damage. Post-Replication Repair (PRR) is the main tolerance pathway bypassing DNA lesions in S-phase. The mechanistic model of PRR involves two sub-pathways: the first is error-prone and related to Translesion DNA Synthesis (TLS), while the second is error-free and acts through template switching processes. The choice among these sub-pathways involves the covalent modification of the Proliferating Cell Nuclear Antigen (PCNA), which functions as a molecular switch. In particular, the mono-ubiquitylation of PCNA drives the PRR pathway to TLS, while PCNA poly-ubiquitylation directs PRR to the error-free sub-pathway. We are exploiting a Systems Biology approach to investigate the PRR sub-pathways, through iterative cross-talks between wet-lab data, mathematical modelling and simulations, to better understand the cellular response to UV-induced DNA damage. This approach is carried out in the Saccharomyces cerevisiae model system using PCNA mono- and poly-ubiquitylation as a readout of the response to increasing UV doses. Time-course experiments reveal that PCNA mono- and poly-ubiquitylated forms are switched off at low UV doses, while at high doses both signals are still present after 5 h. Preliminary simulation data implicate a deubiquitylation mechanism to switch off the PRR signals , but the contribution of additional mechanisms is under evaluation. |
| نوع الوثيقة: |
conference object |
| اللغة: |
English |
| Relation: |
Ubiquitin and ubiquitin-like modifiers: from functional modules to Systems Biology; http://hdl.handle.net/2434/161770 |
| الاتاحة: |
http://hdl.handle.net/2434/161770 |
| رقم الانضمام: |
edsbas.A31C645E |
| قاعدة البيانات: |
BASE |