PMID- 15213235 OWN - NLM STAT- MEDLINE DCOM- 20041006 LR - 20210206 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 279 IP - 35 DP - 2004 Aug 27 TI - DNA repair defects channel interstrand DNA cross-links into alternate recombinational and error-prone repair pathways. PG - 36462-9 AB - The repair of psoralen interstrand cross-links in the yeast Saccharomyces cerevisiae involves the DNA repair groups nucleotide excision repair (NER), homologous recombination (HR), and post-replication repair (PRR). In repair-proficient yeast cells cross-links induce double-strand breaks, in an NER-dependent process; the double-strand breaks are then repaired by HR. An alternate error-prone repair pathway generates mutations at cross-link sites. We have characterized the repair of plasmid molecules carrying a single psoralen cross-link, psoralen monoadduct, or double-strand break in yeast cells with deficiencies in NER, HR, or PRR genes, measuring the repair efficiencies and the levels of gene conversions, crossing over, and mutations. Strains with deficiencies in the NER genes RAD1, RAD3, RAD4, and RAD10 had low levels of cross-link-induced recombination but higher mutation frequencies than repair-proficient cells. Deletion of the HR genes RAD51, RAD52, RAD54, RAD55, and RAD57 also decreased induced recombination and increased mutation frequencies above those of NER-deficient yeast. Strains lacking the PRR genes RAD5, RAD6, and RAD18 did not have any cross-link-induced mutations but showed increased levels of recombination; rad5 and rad6 cells also had altered patterns of cross-link-induced gene conversion in comparison with repair-proficient yeast. Our observations suggest that psoralen cross-links can be repaired by three pathways: an error-free recombinational pathway requiring NER and HR and two PRR-dependent error-prone pathways, one NER-dependent and one NER-independent. FAU - Saffran, Wilma A AU - Saffran WA AD - Department of Chemistry and Biochemistry, Queens College of the City University of New York, 65-30 Kissena Boulevard, Flushing, NY 11367, USA. Wilma_Saffran@qc.edu FAU - Ahmed, Shaila AU - Ahmed S FAU - Bellevue, Sherly AU - Bellevue S FAU - Pereira, Gillian AU - Pereira G FAU - Patrick, Teleka AU - Patrick T FAU - Sanchez, Wendy AU - Sanchez W FAU - Thomas, Sandra AU - Thomas S FAU - Alberti, Marie AU - Alberti M FAU - Hearst, John E AU - Hearst JE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040622 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Cross-Linking Reagents) RN - 0 (DNA, Fungal) RN - 9007-49-2 (DNA) RN - KTZ7ZCN2EX (Ficusin) SB - IM MH - Alleles MH - Cross-Linking Reagents/*pharmacology MH - DNA/metabolism MH - DNA Damage MH - *DNA Repair MH - DNA, Fungal MH - Ficusin/*chemistry/metabolism MH - Models, Biological MH - Models, Genetic MH - Mutagenesis MH - Mutation MH - Phenotype MH - Plasmids/metabolism MH - *Recombination, Genetic MH - Saccharomyces cerevisiae/metabolism EDAT- 2004/06/24 05:00 MHDA- 2004/10/07 09:00 CRDT- 2004/06/24 05:00 PHST- 2004/06/24 05:00 [pubmed] PHST- 2004/10/07 09:00 [medline] PHST- 2004/06/24 05:00 [entrez] AID - S0021-9258(20)85889-X [pii] AID - 10.1074/jbc.M402323200 [doi] PST - ppublish SO - J Biol Chem. 2004 Aug 27;279(35):36462-9. doi: 10.1074/jbc.M402323200. Epub 2004 Jun 22.