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DNA polymerase POLN participates in crosslink repair and homologous recombination

Domenii publicaţii > Biologie + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Moldovan GL, Madhavan MV, Mirchandani KD, McCaffrey RM, Vinciguerra P, D'Andrea AD

Editorial: Mol Cell Biol, 30, p.1088-1096, 2010.


All cells rely on DNA polymerases to duplicate their genetic material and to repair or bypass DNA lesions. In humans, sixteen polymerases have been identified, and each bears specific functions in genome maintenance. Here, we identified the recently discovered polymerase POLN to be involved in repair of DNA crosslinks. 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 crosslink 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 crosslinks.

Cuvinte cheie: DNA repair, Fanconi Anemia, DNA replication, cell cycle regulation, cancer