Inviability of a DNA2 deletion mutant is due to the DNA damage checkpoint

Dna2 is a dual polarity exo/endonuclease, and 5' to 3' DNA helicase involved in Okazaki Fragment Processing (OFP) and Double-Strand Break (DSB) Repair. In yeast, DNA2 is an essential gene, as expected for a DNA replication protein. Suppression of the lethality of dna2 Delta. mutants has been found to occur by two mechanisms: overexpression of RAD27(scFEN1), encoding a 5' to 3' exo/endo nuclease that processes Okazaki fragments (OFs) for ligation, or deletion of PIF1, a 5' to 3' helicase involved in mitochondrial recombination, telomerase inhibition and OFP. Mapping of a novel, spontaneously arising suppressor of dna2 Delta now reveals that mutation of rad9 and double mutation of rad9 mrc1 can also suppress the lethality of dna2. mutants. Interaction of dna2. and DNA damage checkpoint mutations provides insight as to why dna2 Delta is lethal but rad27 Delta is not, even though evidence shows that Rad27(ScFEN1) processes most of the Okazaki fragments, while Dna2 processes only a subset.