INVESTIGADORES
MANSILLA Sabrina Florencia
congresos y reuniones científicas
Título:
Role of p21 on the replication of damage DNA
Autor/es:
SABRINA MANSILLA; GASTON SORIA; MARIA BELEN VALLERGA; JULIANA SPERONI; MARIA BELEN FEDERICO; MARTIN HABIF; VANESA GOTTIFREDI
Lugar:
Montevideo
Reunión:
Workshop; XVII Alexander Hollaender Course: Environmental genetics, epigenetics and genomic instability; 2012
Institución organizadora:
Alexander Hollaender Course
Resumen:
Our
laboratory has found that the cyclin dependent kinase inhibitor p21 is degraded
when cells are challenged with UV light. Different lines of evidences indicated
that p21 degradation could result from the activation of DNA replication
auxiliary mechanisms. In fact, since replicative polymerases cannot accommodate
damage DNA. To avoid cell death, mechanisms such as translesion DNA synthesis,
TLS, aid DNA replication and prevents irreversible stalling. During TLS,
replicative polymerases are replaced by TLS polymerases that bypass DNA
lesions. While many positive regulators of TLS were described, little is known
about the mechanisms of negative regulation of TLS. We have found that PCNA (Proliferating
Cell Nuclear Antigen) binding by p21 impairs the recruitment of
many TLS polymerases to replication foci after UV
irradiation. In line, forced p21 stabilization triggers excessive stalling of DNA
replication and the accumulation of DNA damage markers such as gH2AX and 53BP1.
Moreover, stable p21 expression after UV causes increased cell death. Together
our data suggest that while basal p21 levels might prevent unnecessary loading
of TLS polymerases at replication forks, p21 degradation after UV might promote
cell survival by preventing replication stalling.