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Saberi, A.* ; Hochegger, H.* ; Szuts, D.* ; Lan, L.* ; Yasui, A.* ; Sale, J.E.* ; Taniguchi, Y.* ; Murakawa, Y.* ; Zeng, W.* ; Yokomori, K.* ; Helleday, T.* ; Teraoka, H.* ; Arakawa, H. ; Buerstedde, J.-M. ; Takeda, S.*

RAD18 and poly(ADP-ribose) polymerase independently suppress the access of nonhomologous end joining to double-strand breaks and facilitate homologous recombination-mediated repair.

Mol. Cell. Biol. 27, 2562-2571 (2007)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The Saccharomyces cerevisiae RAD18 gene is essential for postreplication repair but is not required for homologous recombination (HR), which is the major double-strand break (DSB) repair pathway in yeast. Accordingly, yeast rad18 mutants are tolerant of camptothecin (CPT), a topoisomerase I inhibitor, which induces DSBs by blocking replication. Surprisingly, mammalian cells and chicken DT40 cells deficient in Rad18 display reduced HR-dependent repair and are hypersensitive to CPT. Deletion of nonhomologous end joining (NHEJ), a major DSB repair pathway in vertebrates, in rad18-deficient DT40 cells completely restored HR-mediated DSB repair, suggesting that vertebrate Rad18 regulates the balance between NHEJ and HR. We previously reported that loss of NHEJ normalized the CPT sensitivity of cells deficient in poly(ADP-ribose) polymerase 1 (PARP1). Concomitant deletion of Rad18 and PARP1 synergistically increased CPT sensitivity, and additional inactivation of NHEJ normalized this hypersensitivity, indicating their parallel actions. In conclusion, higher-eukaryotic cells separately employ PARP1 and Rad18 to suppress the toxic effects of NHEJ during the HR reaction at stalled replication forks.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0270-7306
e-ISSN 1098-5549
Quellenangaben Band: 27, Heft: 7, Seiten: 2562-2571 Artikelnummer: , Supplement: ,
Verlag American Society for Microbiology (ASM)
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Radiation Biology (IMS)