IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A novel kinase-independent function of Chk1 in the replication of damaged DNA
Autor/es:
MARTIN HABIF; JULIANA SPERONI; SABRINA F MANSILLA; MARÍA BELÉN FEDERICO; MARÍA BELÉN VALLERGA; VANESA GOTTIFREDI
Lugar:
Montevideo
Reunión:
Simposio; XVII ALEXANDER HOLLAENDER COURSE, ?Environmental Genetics, Epigenetics and Genomic Instability?; 2012
Institución organizadora:
Instituto de Investigaciones Biológicas Clemente Estable
Resumen:
The checkpoint kinases Chk1 and ATR are broadly known for their role in the response to the accumulation of damaged DNA. Since Chk1 activation requires its phosphorylation by ATR, it is expected that ATR or Chk1 downregulation should cause similar alterations in the signals triggered by DNA lesions. Intriguingly, we found that Chk1 -but not ATR- promotes the progression of replication forks after UV irradiation. Strikingly, this novel role of Chk1 is independent of its kinase-domain and of its partnership with Claspin, and entirely relies on its recently identified PCNA-interacting motif, required for its release from chromatin after DNA damage. Supporting the importance of Chk1 release, a chromatin immobilized histone-H2B-Chk1 chimera, was unable to promote replication of damaged DNA. Moreover, inefficient chromatin dissociation of Chk1 impaired the recruitment of the translesion synthesis (TLS) DNA polymerase ƞ to replication foci after UV. These findings unveil an unforeseen facet of Chk1 exclusively associated to the maintenance of active replication forks after UV irradiation, in a manner in which Chk1 release prompts TLS to avoid replication stalling.