Cell Cycle Regulation of a DNA Ligase-encoding Gene (CaLIG4) from Candida Albicans

A DNA ligase (CaLIG4) (formerly CaCDC9) of the human pathogen, Candida albicans, has been characterized. The encoded protein displayed a significant similarity to ligase IV from both Saccharomyces cerevisiae and humans. In addition, whereas CaLIG4 did not complement a S. cerevisiae cdc9 mutant, it re-established non-homologous end-joining of DNA double-strand breaks in a S. cerevisiae lig4 deletant. CaLIG4 was assigned to chromosome 2. Several cis-acting effector sequences were identified in the promoter region of the CaLIG4, including the DNA sequence element ACGNG, which is required for periodic transcription of several DNA-replicating genes in S. cerevisiae. The level of transcription of CaLIG4 in C. albicans varies during the yeast cell cycle. Newly formed cells contained basal levels of transcript which increased to a maximum level when cells were in late G(1). Thereafter, levels of transcript dropped as DNA replication was initiated. Our results suggest that CaLIG4 may perform an important role during the mitotic cycle of C. albicans.