Homologous recombination in Candida albicans:: role of CaRad52p in DNA repair, integration of linear DNA fragments and telomere length

被引:49
作者
Ciudad, T
Andaluz, E
Steinberg-Neifach, O
Lue, NF
Gow, NAR
Calderone, RA
Larriba, G [1 ]
机构
[1] Univ Extremadura, Fac Ciencias, Dept Microbiol, E-06071 Badajoz, Spain
[2] Cornell Univ, Weill Med Coll, WR Hearst Microbiol Res Ctr, Dept Microbiol & Immunol, New York, NY 10021 USA
[3] Univ Aberdeen, Inst Med Sci, Sch Med Sci, Aberdeen AB25 2ZD, Scotland
[4] Georgetown Univ, Sch Med, Dept Microbiol & Immunol, Washington, DC 20007 USA
关键词
D O I
10.1111/j.1365-2958.2004.04197.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Carad52Delta/Carad52Delta 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.
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页码:1177 / 1194
页数:18
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