Human DNA Polymerase ϵ Is Able to Efficiently Extend from Multiple Consecutive Ribonucleotides
Year: 2012
Type: article
Abstract: Replicative DNA polymerases (Pols) help to maintain the high fidelity of replication in large part through their strong selectivity against mispaired deoxyribonucleotides. It has recently been demonstrated that several replicative Pols from yeast have surprisingly low selectivity for deoxyribonucleotides over their analogous ribonucleotides. In human cells, ribonucleotides are found in great abundance over deoxyribonucleotides, raising the possibility that ribonucleotides are incorporated in the human genome at significant levels during normal cellular functions. To address this possibility, the ability of human DNA polymerase ε to incorporate ribonucleotides was tested. At physiological concentrations of nucleotides, human Pol ε readily inserts and extends from incorporated ribonucleotides. Almost half of inserted ribonucleotides escape proofreading by 3' → 5' exonuclease-proficient Pol ε, indicating that ribonucleotide incorporation by Pol ε is likely a significant event in human cells. Human Pol ε is also efficient at extending from primers terminating in up to five consecutive ribonucleotides. This efficient extension appears to result from reduced exonuclease activity on primers containing consecutive 3'-terminal ribonucleotides. These biochemical properties suggest that Pol ε is a likely source of ribonucleotides in human genomic DNA.
Source: Journal of Biological Chemistry
Institutions: Tulane University, The Ohio State University
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W2079544086