Yes, don't forget the TELOMERES!

• October 2013
• > Vannier et al., 342 (6155): 239-242

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RTEL1 Is a Replisome-Associated Helicase That Promotes Telomere and Genome-Wide Replication

1. Jean-Baptiste Vannier¹,*,
2. Sumit Sandhu²,*,
3. Mark IR. Petalcorin¹,
4. Xiaoli Wu²,
5. Zinnatun Nabi²,
6. Hao Ding²,³,^†,
7. Simon J. Boulton¹,^†

+ Author Affiliations

1. ¹DNA Damage Response laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms EN6 3LD, UK.
2. ²Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3E 3J7, Canada.
3. ³Manitoba Institute of Child Health, Winnipeg, Manitoba, R3E 3P4, Canada.

1. ↵†Corresponding author. E-mail: dingh@cc.umanitoba.ca (H.D.); simon.boulton@cancer.org.uk (S.J.B.)

1. ↵* These authors contributed equally to this work.

• Abstract
• Editor's Summary

Regulator of telomere length 1 (RTEL1) is an essential DNA helicase that disassembles telomere loops (T loops) and suppresses telomere fragility to maintain the integrity of chromosome ends. We established that RTEL1 also associates with the replisome through binding to proliferating cell nuclear antigen (PCNA). Mouse cells disrupted for the RTEL1-PCNA interaction (PIP mutant) exhibited accelerated senescence, replication fork instability, reduced replication fork extension rates, and increased origin usage. Although T-loop disassembly at telomeres was unaffected in the mutant cells, telomere replication was compromised, leading to fragile sites at telomeres. RTEL1-PIP mutant mice were viable, but loss of the RTEL1-PCNA interaction accelerated the onset of tumorigenesis in p53-deficient mice. We propose that RTEL1 plays a critical role in both telomere and genome-wide replication, which is crucial for genetic stability and tumor avoidance.
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