INVESTIGADORES
MANSILLA Sabrina Florencia
congresos y reuniones científicas
Título:
NOVEL REGULATORS OF THE REPLICATION OF DAMAGED DNA
Autor/es:
SABRINA MANSILLA; JULIANA SPERONI; MARIA BELEN FEDERICO; MARIA BELEN VALLERGA; MARTIN HABIF; VANESA GOTTIFREDI
Lugar:
San Luis, Potrero de los Funes
Reunión:
Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.; 2011
Institución organizadora:
SAIB
Resumen:
While it is clear that DNA lesions trigger the
activation of many signalling pathways that aid DNA replication, the levels of coordination
between such pathways are unknown. On one hand, stalled forks trigger the
activation of checkpoint signals to globally reduce DNA synthesis. On the other
hand, translesion DNA synthesis (TLS) avoids fork stalling using DNA lesions as
templates. While TLS promotes the maintenance of DNA replication on individual
replicating forks, one single stalling event spreads a checkpoint-induced warning
signal to other replicating forks. Both pathways are activated in the same
cells but it is unknown if they can coordinate their action at single
replicating forks. We have recently found that two molecules associated to
checkpoint activation can influence TLS activation. We have accumulated evidence
indicating that a checkpoint target, the cyclin kinases inhibitor p21, is a
negative regulator of TLS associated events. Also, we have found that a central
checkpoint effector kinase, Chk1, positively modulates the same events.
Intriguingly the PCNA
domain of both proteins is required for their action on TLS. Thus, we propose
that the crosstalk between molecules in both pathways might determine the
timing of their activation at forks that encounter DNA lesions.