Tipin/Tim1/And1 protein complex promotes Pola 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 r...

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Bibliographic Details
Published in:The EMBO journal 2009-12, Vol.28 (23), p.3681-3692
Main Authors: Errico, Alessia, Cosentino, Claudia, Rivera, Teresa, Losada, Ana, Schwob, Etienne, Hunt, Tim, Costanzo, Vincenzo
Format: Article
Language:English
Subjects:
Xenopus laevis
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Summary: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 Pola on chromatin. We identified And1, a Pola chromatin-loading factor, as new Tipin-binding partner. We found that both Tipin and And1 promote stable binding of Pola 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.
ISSN:0261-4189
DOI:10.1038/emboj.2009.304