Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion.

ABSTRACT: The Timeless-Tipin protein complex has been reported to be important for replication checkpoint and normal DNA replication processes. However, the precise mechanisms by which Timeless-Tipin preserves genomic integrity are largely unclear. Here, we describe the roles of Timeless-Tipin in replication fork stabilization and sister chromatid cohesion. We show in human cells that Timeless is recruited to replication origin regions and dissociate from them as replication proceeds. Cdc45, which is known to be required for replication fork progression, shows similar patterns of origin association to those of Timeless. Depletion of Timeless-Tipin causes chromosome fragmentation and defects in damage repair in response to fork collapse, suggesting that it is required for replication fork maintenance

SUBMITTER: Leman AR 

PROVIDER: S-EPMC2823575 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature