Paul, Shilpi, Rebok, Abbey, Cifani, Paolo, Paul, Anirban, Pappin, Darryl, Huang, Tony, Spratt, Thomas (2022) Translesion DNA synthesis polymerase κ is essential to a carcinogen-induced nucleolar stress response. bioRxiv. (Submitted)
Abstract
DNA polymerase kappa (Polκ) has multiple cellular roles such as translesion DNA synthesis, replication of repetitive sequences and nucleotide excision repair. Since all polymerases insert the canonical deoxynucleotide triphosphates, it is difficult to determine which polymerase is active at a particular genomic site. To counter this difficulty, we utilized the selective Polκ substrate, N2-(4-ethynylbenyl)-2’-deoxyguanosine (EBndG), as bait to capture proteins associated with Polκ synthesized DNA. Here we show that, Polκ is active in the nucleolus and Polκ synthesized DNA are enriched with nucleolar proteins. Exposure of cells to benzo[a]pyrene diol epoxide (BPDE) increases Polκ stability and induces hallmarks of nucleolar stress. The expression and activity of Polκ is regulated by the polycomb complex protein Ring Finger Protein 2 (RNF2) and by the PARylation by poly(ADP)-ribose polymerase 1 (PARP1). This study provides insight into the novel role of Polκ in the nucleolus and in maintaining ribosomal DNA integrity after BPDE damage.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > DNA polymerase bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types |
| CSHL Authors: | |
| Communities: | CSHL labs > Pappin lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 2022 |
| Date Deposited: | 28 Sep 2023 16:10 |
| Last Modified: | 16 Jan 2024 21:03 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41026 |
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