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Homologous recombination in Candida albicans : role of CaRad52p in DNA repair, integration of linear DNA fragments and telomere length
Author(s) -
Ciudad Toni,
Andaluz Encarnación,
SteinbergNeifach Olga,
Lue Neal F.,
Gow Neil A. R.,
Calderone Richard A.,
Larriba Germán
Publication year - 2004
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2004.04197.x
Subject(s) - biology , telomere , homologous recombination , recombination , dna , genetics , candida albicans , homologous chromosome , dna repair , gene
Summary Chromosomal rearrangements are common in both clinical isolates and spontaneous mutants of Candida albicans . It appears that many of these rearrangements are caused by translocations around the major sequence repeat (MSR) that is present in all chromosomes except chromosome 3, suggesting that homologous recombination (HR) may play an important role in the survival of this organism. In order to gain information on these processes, we have cloned the homologue of RAD52 , which in Saccharomyces cerevisiae is the only gene required for all HR events. CaRAD52 complemented poorly a rad52 mutant of S. cerevisiae . Two null Carad52 Δ/ Carad52 Δ mutants were constructed by sequential deletion of both alleles and two reconstituted strains were obtained by reintegration of the gene. Characterization of these mutants indicated that HR plays an essential role in the repair of DNA lesions caused by both UV light and the radiomimetic compound methyl‐methane‐sulphonate (MMS), whereas the non‐homologous end‐joining pathway (NHEJ) is used only in the absence of Rad52p or after extensive DNA damage. Repair by HR is more efficient in exponentially growing than in stationary cells, probably because a larger number of cells are in late S or G 2 phases of the cell cycle (and therefore, can use a sister chromatid as a substrate for recombinational repair), whereas stationary phase cells are mainly in G 0 or G 1 , and only can be repaired using the chromosomal homologue. In addition, CaRad52p is absolutely required for the integration of linear DNA with long flanking homologous sequences. Finally, the absence of CaRad52p results in the lengthening of telomeres, even in the presence of an active telomerase, an observation not described in any other organism. This raises the possibility that both telomerase and homologous recombination may function simultaneously at C. albicans telomeres.