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Genetic control of predominantly error-free replication through an acrolein-derived minor-groove DNA adduct
| Content Provider | Scilit |
|---|---|
| Author | Yoon, Jung-Hoon Hodge, Richard P. Hackfeld, Linda C. Park, Jeseong Choudhury, Jayati Roy Prakash, Satya Prakash, Louise |
| Copyright Year | 2018 |
| Description | Journal: Journal of Biological Chemistry Acrolein, an α,β-unsaturated aldehyde, is generated in vivo as the end product of lipid peroxidation and from metabolic oxidation of polyamines, and it is a ubiquitous environmental pollutant. The reaction of acrolein with the N2 of guanine in DNA leads to the formation of $γ-hydroxy-1-N^{2}$-propano-2′ deoxyguanosine (γ-HOPdG), which can exist in DNA in a ring-closed or a ring-opened form. Here, we identified the translesion synthesis (TLS) DNA polymerases (Pols) that conduct replication through the permanently ring-opened reduced form of γ-HOPdG ((r) γ-HOPdG) and show that replication through this adduct is mediated via Rev1/Polη-, Polι/Polκ-, and Polθ-dependent pathways, respectively. Based on biochemical and structural studies, we propose a role for Rev1 and Polι in inserting a nucleotide (nt) opposite the adduct and for Pols η and κ in extending synthesis from the inserted nt in the respective TLS pathway. Based on genetic analyses and biochemical studies with Polθ, we infer a role for Polθ at both the nt insertion and extension steps of TLS. Whereas purified Rev1 and Polθ primarily incorporate a C opposite (r) γ-HOPdG, Polι incorporates a C or a T opposite the adduct; nevertheless, TLS mediated by the Polι-dependent pathway as well as by other pathways occurs in a predominantly error-free manner in human cells. We discuss the implications of these observations for the mechanisms that could affect the efficiency and fidelity of TLS Pols. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827445/pdf http://www.jbc.org/content/293/8/2949.full.pdf |
| Ending Page | 2958 |
| Page Count | 10 |
| Starting Page | 2949 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.ra117.000962 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 8 |
| Volume Number | 293 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2018-02-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology (r) Gamma-hopdg Phosphoramidite Synthesis Dna Damage Response Translesion Synthesis in Human Cells |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
