Analysing the contribution of ATM/ATR pathway activation in establishing the premature senescence of E2F1/E2F2-/- bone-marrow-derived macrophages
Contribuinte(s) |
Iglesias Ara, Ainhoa F. CIENCIA Y TECNOLOGIA ZIENTZIA ETA TEKNOLOGIA F. Genética, Antropología Física y Fisiología Animal;;Genetika, Antropologia Fisikoa eta Animalien Fisiologia Grado en Bioquímica y Biología Molecular Biokimikako eta Biologia Molekularreko Gradua |
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Data(s) |
01/04/2015
01/04/2015
01/04/2015
20/06/2014
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Resumo |
E2F1 and E2F2 transcription factors have an important role during the regulation of cell cycle. In experiments done with E2F1/E2F2 knockout mice, it has been described that bone-marrow-derived macrophages (BMDM) undergo an early rapid proliferation event related to DNA hyper-replication. As a consequence, DNA damage response (DDR) pathway is triggered and E2F1/E2F2 knockout macrophages enter premature senescence related to G2/M phase arrest. The exact mechanism trough which DNA hyper-replication leads to DDR in absence of E2F1 and E2F2 remains undiscovered. To determine whether the ATR/ATM pathway, the master regulator of G2/M checkpoint, might be the surveillance mechanism in order to regulate uncontrolled proliferation in the DKO model, we monitored and analysis biochemical properties of BMDM cultures in the presence of caffeine, a potent inhibitor of ATM/ATR activity. Our results show that the addition of caffeine abolishes premature senescence in DKO BMDM, stimulates γ-H2AX accumulation and decreases Mcm2 expression. |
Identificador |
http://hdl.handle.net/10810/14847 51830-631146-10 8206-631146 |
Idioma(s) |
eng en |
Direitos |
© 2014, EL AUTOR info:eu-repo/Semantics/openAccess |
Palavras-Chave | #E2F1/E2F2-/- #caffeine #ATM/ATR |
Tipo |
info:eu-repo/semantics/bachelorThesis |