Tipin/Tim1/And1 protein complex promotes Pol alpha chromatin binding and sister chromatid cohesion.
The Tipin/Tim1 complex plays an important role in the S-phase checkpoint and replication fork stability. However, the biochemical function of this complex is poorly understood. Using Xenopus laevis egg extract we show that Tipin is required for DNA replication in the presence of limiting amount of replication origins. Under these conditions the DNA replication defect correlates with decreased levels of DNA Polalpha on chromatin. We identified And1, a Polalpha chromatin-loading factor, as new Tipin-binding partner. We found that both Tipin and And1 promote stable binding of Polalpha to chromatin and that this is required for DNA replication under unchallenged conditions. Strikingly, extracts lacking Tipin and And1 also show reduced sister chromatids cohesion. These data indicate that Tipin/Tim1/And1 form a complex that links stabilization of replication fork and establishment of sister chromatid cohesion.
Errico
Alessia
A
Genome Stability and Cell Cycle Control Groups, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts, UK.
Cosentino
Claudia
C
Rivera
Teresa
T
Losada
Ana
A
Schwob
Etienne
E
Hunt
Tim
T
Costanzo
Vincenzo
V
D002352:Carrier Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004256:DNA Polymerase I / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D011485:Protein Binding / Q000235:genetics; D055550:Protein Stability; D018741:Replication Origin / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000235:genetics; D029867:Xenopus Proteins / Q000502:physiology*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C524403:Tim1 protein, Xenopus; C106931:WDHD1 protein, Xenopus; D029867:Xenopus Proteins; C524402:tipin protein, Xenopus; D004256:DNA Polymerase I