POLE proofreading defects: Contributions to mutagenesis and cancer

DNA Repair
Vivian S Park, Zachary F Pursell

Abstract

DNA polymerases are uniquely poised to contribute to the elevated mutation burdens seen in many human tumors. These mutations can arise through a number of different polymerase-dependent mechanisms, including intrinsic errors made using template DNA and precursor dNTPs free from chemical modifications, misinsertion events opposite chemically damaged template DNA or insertion events using modified nucleotides. While specific DNA repair polymerases have been known to contribute to tumorigenesis, the role of replication polymerases in mutagenesis in human disease has come into sharp focus over the last decade. This review describes how mutations in these replication DNA polymerases help to drive mutagenesis and tumor development, with particular attention to DNA polymerase epsilon. Recent studies using cancer genome sequencing, mutational signature analyses, yeast and mouse models, and the influence of mismatch repair on tumors with DNA polymerase mutations are discussed.

Citations

Nov 15, 2020·Bulletin du cancer·Jacques Robert
Nov 24, 2019·Gynecologic Oncology·Marina StasenkoKaren A Cadoo
Nov 17, 2020·Frontiers in Oncology·Shiqin LiHan-Xiang An
Feb 14, 2021·Journal of Huntington's Disease·Amit L DeshmukhChristopher E Pearson
Oct 15, 2020·The Journal of Biological Chemistry·Walter J Zahurancik, Zucai Suo
Jan 18, 2021·The Journal of Biological Chemistry·Walter J Zahurancik, Zucai Suo
Mar 30, 2021·Frontiers in Oncology·Zhu ZengZhengyin Liao
May 11, 2021·Frontiers in Oncology·Hong YuanJun Zhang
Dec 8, 2021·Personalized Medicine·Arianna OttiniGiuseppe Procopio

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.