TY - JOUR
T1 - Detours to replication
T2 - Functions of specialized DNA polymerases during oncogene-induced replication stress
AU - Tsao, Wei Chung
AU - Eckert, Kristin A.
N1 - Funding Information:
Funding: Research in our laboratory was supported by supported by NIH grant R01-GM087472, the Donald B. and Dorothy L. Stabler Foundation, and generous donations to the Jake Gittlen Cancer Research Foundation.
Funding Information:
Research in our laboratory was supported by supported by NIH grant R01-GM087472, the Donald B. and Dorothy L. Stabler Foundation, and generous donations to the Jake Gittlen Cancer Research Foundation.
Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/10/20
Y1 - 2018/10/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85055141883&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055141883&partnerID=8YFLogxK
U2 - 10.3390/ijms19103255
DO - 10.3390/ijms19103255
M3 - Review article
C2 - 30347795
AN - SCOPUS:85055141883
SN - 1661-6596
VL - 19
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 10
M1 - 3255
ER -