Originally published as Genetics Published Articles Ahead of Print on February 3, 2008.

Genetics, Vol. 178, 1169-1176, March 2008, Copyright © 2008
doi:10.1534/genetics.107.079483

Dominant Suppression of Repeat-Induced Point Mutation in Neurospora crassa by a Variant Catalytic Subunit of DNA Polymerase-{zeta}

Ranjan Tamuli and Durgadas P. Kasbekar1

Centre for Cellular and Molecular Biology, Hyderabad 500 007, India

1 Corresponding author: Centre for Cellular and Molecular Biology, Uppal Rd., Hyderabad 500 007, India.
E-mail: kas{at}ccmb.res.in

Crosses involving the Adiopodoumé strain of Neurospora crassa are defective for repeat-induced point mutation (RIP), a genome defense mechanism of fungi. We show here that the Adiopodoumé strain possesses an incompletely penetrant and variably expressive dominant suppressor of RIP (Srp) that maps to an ~34-kbp genome segment that is ~26 kbp proximal to mat on linkage group IL. Gene disruption experiments revealed that Srp is the upr-1 allele of Adiopodoumé (upr-1Ad) that is contained within this segment. The upr-1 gene codes for the catalytic subunit of the translesion DNA polymerase-{zeta} (Pol-{zeta}) and it is unusually polymorphic in Neurospora. That the upr-1 gene contains upstream ORFs that overlap with the main ORF is potentially relevant to the incomplete penetrance and variable expressivity of the suppressor. Crosses between heterokaryons that contain upr-1Ad and strains that prevent mating events involving nuclei that contain upr-1Ad yielded no progeny in which RIP had occurred, consistent with the idea that the suppressor encoded by upr-1Ad is diffusible. The potential involvement of the Pol-{zeta} subunit in two functions, translesion DNA synthesis and RIP regulation, might account for the rapid evolution of its gene in Neurospora.