Analysing the contribution of ATM/ATR pathway activation in establishing the premature senescence of E2F1/E2F2-/- bone-marrow-derived macrophages


Autoria(s): Zuazo Gaztelu, Iratxe
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

Data(s)

01/04/2015

01/04/2015

01/04/2015

20/06/2014

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