Open AccessDNA Polymerase POLN Participates in Cross-Link Repair and Homologous Recombination
Author(s) -
GeorgeLucian Moldovan,
Mahesh V. Madhavan,
Kanchan D. Mirchandani,
Ryan McCaffrey,
Patrizia Vinciguerra,
Alan D. D’Andrea
Publication year - 2010
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.01124-09
Subject(s) - biology , homologous recombination , dna repair , dna polymerase , genetics , helicase , replication protein a , polymerase , dna polymerase ii , homologous chromosome , dna , microbiology and biotechnology , gene , dna binding protein , polymerase chain reaction , reverse transcriptase , rna , transcription factor
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 theDrosophila 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.