title: DNA polymerase POLN participates in cross-link repair and homologous recombination.
abstract: All cells rely on DNA polymerases to duplicate their genetic material and to repair or bypass DNA lesions. In humans, 16 polymerases have been identified, and each bears specific functions in genome maintenance. We identified here the recently discovered polymerase POLN to be involved in repair of DNA cross-links. Such DNA lesions are highly toxic and are believed to be repaired by the sequential activity of nucleotide excision repair, translesion synthesis, and homologous recombination mechanisms. By functionally assaying its role in these processes, we unraveled an unexpected involvement of POLN in homologous recombination. Moreover, we obtained evidence for physical and functional interaction of POLN with factors belonging to the Fanconi anemia pathway, a master regulator of cross-link repair. Finally, we show that POLN interacts and cooperates in DNA repair with the helicase HEL308, which shares a common origin with POLN in the Drosophila mus308 gene. Our data indicate that this novel polymerase-helicase complex participates in homologous recombination repair and is essential for cellular protection against DNA cross-links.
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02215, USA.
authors.forename: George-Lucian
authors.initials: GL
authors.lastname: Moldovan
authors.forename: Mahesh V
authors.initials: MV
authors.lastname: Madhavan
authors.forename: Kanchan D
authors.initials: KD
authors.lastname: Mirchandani
authors.forename: Ryan M
authors.initials: RM
authors.lastname: McCaffrey
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vinciguerra
authors.forename: Alan D
authors.initials: AD
authors.lastname: D'Andrea
mesh_terms: D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D051135:Rad51 Recombinase / Q000378:metabolism; D011995:Recombination, Genetic
chemical_list: C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D004247:DNA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D004259:DNA-Directed DNA Polymerase; C546205:POLN protein, human; D004265:DNA Helicases