Timeless protection of telomeres
The DNA replication machinery encounters problems at numerous genomic regions that are inherently difficult to replicate. These genomic regions include telomeres, which contain repetitive DNA and telomere-binding proteins. If not properly regulated, replication of such genomic regions can result in DNA damage, leading to genomic instability. Studies implicated a role of Timeless-related proteins at difficult-to-replicate genomic regions, including telomeres. However, how these proteins maintain telomeres was elusive. In a recent report, we described the role of Swi1, a Timeless-related protein, in telomere maintenance in fission yeast. We demonstrated that Swi1 is required for proper replication of repeat DNA sequences at telomeres. We also showed that Swi1-deficient cells utilize recombination-based ALT (alternative lengthening of telomeres)-like mechanisms to maintain telomeres in the absence of telomerase. Here, we highlight these findings and present additional data to discuss the role of Swi1Timeless in telomere protection and ALT prevention.
KeywordsSwi1 Timeless FPC Fork protection complex Telomeres Myb/SANT Tbf1 ALT Alternative lengthening of telomeres Replication fork Genomic integrity Repeat DNA Cancer
This work was supported by the Aging Initiative at Drexel University College of Medicine. We thank Chiaki Noguchi and Grant Grothusen for technical assistance and National BioResource Project Japan for S. pombe strains.
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