Dominant suppression of repeat-induced point mutation in Neurospora crassa by a variant catalytic subunit of DNA polymerase zeta

DNA聚合酶ζ变体催化亚基对粗糙脉孢菌中重复序列诱导的点突变的显性抑制

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Abstract

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 approximately 34-kbp genome segment that is approximately 26 kbp proximal to mat on linkage group IL. Gene disruption experiments revealed that Srp is the upr-1 allele of Adiopodoumé (upr-1(Ad)) 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-1(Ad) and strains that prevent mating events involving nuclei that contain upr-1(Ad) yielded no progeny in which RIP had occurred, consistent with the idea that the suppressor encoded by upr-1(Ad) 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.

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