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Updated: Jul 22, 2025

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
The TIMELESS Roles in Genome Stability and Beyond
Sameera Vipat1, Tatiana N Moiseeva1
1Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn 12618, Estonia.
Abstract:
TIMELESS protein (TIM) protects replication forks from stalling at difficult-to-replicate regions and plays an important role in DNA damage response, including checkpoint signaling, protection of stalled replication forks and DNA repair. Loss of TIM causes severe replication stress, while its overexpression is common in various types of cancer, providing protection from DNA damage and resistance to chemotherapy. Although TIM has mostly been studied for its part in replication stress response, its additional roles in supporting genome stability and a wide variety of other cellular pathways are gradually coming to light. This review discusses the diverse functions of TIM and its orthologs in healthy and cancer cells, open questions, and potential future directions.
Insights
TIMELESS protein (TIM) guards against replication fork stalling and aids DNA damage response. Its roles in cancer cells, including DNA protection and chemotherapy resistance, are increasingly recognized.
Area of Science:
- Molecular Biology
- Cellular Biology
- Cancer Research
Background:
- TIMELESS protein (TIM) is crucial for protecting replication forks from stalling.
- TIM is involved in DNA damage response, checkpoint signaling, and DNA repair.
- TIM loss causes replication stress, while its overexpression is linked to cancer, conferring chemoresistance.
Purpose of the Study:
- To review the diverse functions of TIMELESS protein and its orthologs.
- To explore TIM's roles in both healthy and cancerous cells.
- To highlight open questions and future research directions for TIM.
Main Methods:
- Literature review of TIMELESS protein functions.
- Analysis of TIM's role in replication stress and DNA damage response.
- Examination of TIM's implications in cancer biology and therapeutic resistance.
Main Results:
- TIM protects replication forks at challenging genomic regions.
- TIM's functions extend beyond replication stress to genome stability and other cellular pathways.
- TIM overexpression in cancer contributes to DNA damage protection and chemotherapy resistance.
Conclusions:
- TIMELESS protein has multifaceted roles in maintaining genome stability.
- Understanding TIM's diverse functions is critical for cancer research and therapy.
- Further investigation into TIM's pathways may reveal new therapeutic strategies.
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