INVESTIGADORES
MANSILLA Sabrina Florencia
congresos y reuniones científicas
Título:
A novel kinase-independent function of Chk1 in the replication of damaged DNA
Autor/es:
JULIANA SPERONI; SABRINA MANSILLA; MARIA BELEN FEDERICO; MARTIN HABIF; VANESA GOTTIFREDI
Lugar:
Nueva York
Reunión:
Conferencia; Cold Spring Harbor meeting on Eukaryotic DNA Replication & Genome Maintenance; 2011
Institución organizadora:
Cold Spring Harbor
Resumen:
Chk1 is broadly known as a central kinase
involved in the cell cycle response to the accumulation of damaged DNA. The
kinase activity of Chk1 is also essential for unperturbed DNA replication. The
activation of Chk1 is totally dependent on its phosphorylation by ATR and in
general, the negative regulation of ATR or Chk1 cause similar consequences in
cells. Intriguingly, using DNA combing technology and specific siRNA-dependent
downregulation, we have observed that Chk1 contribution to the maintenance of
fork progression after an UV insult is more robust when compared to ATR. In
line with this, we found that the kinase domain of Chk1 is not required for the
maintenance of fork progression immediately after UV irradiation. Instead, a
recently identified motif of Chk1 involved in its release from chromatin is
necessary to maintain replication fork progression after UV-induced DNA damage.
Moreover, this motif of Chk1 also promotes the organization of the specialized
polymerase pol h into subnuclear focal structures.
This is particularly interesting since pol h sustains DNA synthesis by using
UV-damaged DNA as templates for replication. Together, our data put forward a
potential kinase-independent contribution of Chk1 to the replication of damaged
DNA.