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Detours to Replication: Functions of Specialized DNA Polymerases during Oncogene-induced Replication Stress

Department of Pathology, The Jake Gittlen Laboratories for Cancer Research, Hershey, PA 17033, USA
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(10), 3255; https://doi.org/10.3390/ijms19103255
Received: 8 September 2018 / Revised: 15 October 2018 / Accepted: 15 October 2018 / Published: 20 October 2018
(This article belongs to the Special Issue DNA Replication Stress)
Incomplete and low-fidelity genome duplication contribute to genomic instability and cancer development. Difficult-to-Replicate Sequences, or DiToRS, are natural impediments in the genome that require specialized DNA polymerases and repair pathways to complete and maintain faithful DNA synthesis. DiToRS include non B-DNA secondary structures formed by repetitive sequences, for example within chromosomal fragile sites and telomeres, which inhibit DNA replication under endogenous stress conditions. Oncogene activation alters DNA replication dynamics and creates oncogenic replication stress, resulting in persistent activation of the DNA damage and replication stress responses, cell cycle arrest, and cell death. The response to oncogenic replication stress is highly complex and must be tightly regulated to prevent mutations and tumorigenesis. In this review, we summarize types of known DiToRS and the experimental evidence supporting replication inhibition, with a focus on the specialized DNA polymerases utilized to cope with these obstacles. In addition, we discuss different causes of oncogenic replication stress and its impact on DiToRS stability. We highlight recent findings regarding the regulation of DNA polymerases during oncogenic replication stress and the implications for cancer development. View Full-Text
Keywords: Difficult-to-Replicate Sequences; replication stress; non-B DNA; Polymerase eta; Polymerase kappa; genome instability; common fragile sites; Microsatellites Difficult-to-Replicate Sequences; replication stress; non-B DNA; Polymerase eta; Polymerase kappa; genome instability; common fragile sites; Microsatellites
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MDPI and ACS Style

Tsao, W.-C.; Eckert, K.A. Detours to Replication: Functions of Specialized DNA Polymerases during Oncogene-induced Replication Stress. Int. J. Mol. Sci. 2018, 19, 3255.

AMA Style

Tsao W-C, Eckert KA. Detours to Replication: Functions of Specialized DNA Polymerases during Oncogene-induced Replication Stress. International Journal of Molecular Sciences. 2018; 19(10):3255.

Chicago/Turabian Style

Tsao, Wei-Chung; Eckert, Kristin A. 2018. "Detours to Replication: Functions of Specialized DNA Polymerases during Oncogene-induced Replication Stress" Int. J. Mol. Sci. 19, no. 10: 3255.

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