| First Author | Takata KI | Year | 2017 |
| Journal | PLoS Genet | Volume | 13 |
| Issue | 6 | Pages | e1006818 |
| PubMed ID | 28570559 | Mgi Jnum | J:241704 |
| Mgi Id | MGI:5903478 | Doi | 10.1371/journal.pgen.1006818 |
| Citation | Takata KI, et al. (2017) Analysis of DNA polymerase nu function in meiotic recombination, immunoglobulin class-switching, and DNA damage tolerance. PLoS Genet 13(6):e1006818 |
| abstractText | DNA polymerase nu (pol nu), encoded by the POLN gene, is an A-family DNA polymerase in vertebrates and some other animal lineages. Here we report an in-depth analysis of pol nu-defective mice and human cells. POLN is very weakly expressed in most tissues, with the highest relative expression in testis. We constructed multiple mouse models for Poln disruption and detected no anatomic abnormalities, alterations in lifespan, or changed causes of mortality. Mice with inactive Poln are fertile and have normal testis morphology. However, pol nu-disrupted mice have a modestly reduced crossover frequency at a meiotic recombination hot spot harboring insertion/deletion polymorphisms. These polymorphisms are suggested to generate a looped-out primer and a hairpin structure during recombination, substrates on which pol nu can operate. Pol nu-defective mice had no alteration in DNA end-joining during immunoglobulin class-switching, in contrast to animals defective in the related DNA polymerase theta (pol theta). We examined the response to DNA crosslinking agents, as purified pol nu has some ability to bypass major groove peptide adducts and residues of DNA crosslink repair. Inactivation of Poln in mouse embryonic fibroblasts did not alter cellular sensitivity to mitomycin C, cisplatin, or aldehydes. Depletion of POLN from human cells with shRNA or siRNA did not change cellular sensitivity to mitomycin C or alter the frequency of mitomycin C-induced radial chromosomes. Our results suggest a function of pol nu in meiotic homologous recombination in processing specific substrates. The restricted and more recent evolutionary appearance of pol nu (in comparison to pol theta) supports such a specialized role. |
