A replication stress safeguard provided by the Elg1 Replication Factor C-like complex.

The Elg1 Replication Factor C-like complex (Elg1-RLC) that functions as a proliferating cell nuclear antigen (PCNA) unloader, is known to be involved in multiple DNA replication/repair-related activities from yeast to humans. By exploiting disassembly prone PCNA mutants, we reveal that Elg1-RLC uses its PCNA unloading activity to counter the DNA-alkylating ...
agent methyl-methanesulfonate (MMS)-mediated slow progression of replication forks (RFs). Despite having a largely functional DNA damage response (DDR), the viability loss of elg1?-DDR double mutants, in the presence of MMS, matches that of mec1? and rad53? cells, deficient for the central checkpoint kinases. This suggests that elg1?-DDR double mutants experience RF collapse when exposed to MMS. Indeed, in response to MMS, accumulation of Rad52 foci in the replicative elg1?-DDR cells supports this possibility. However, the failure of rescuing elg1?-DDR mutants by elevating deoxynucleoside triphosphate (dNTP) levels (by deleting the ribonucleotide reductase SML1) eliminates the possibility of a Rad53-regulated dNTP shortage-mediated fork collapse. Thus, we propose an S-phase checkpoint regulatory role of Elg1-RLC that works through a noncanonical pathway parallel to the canonical one. Collectively, our findings suggest a model in which Elg1-RLC, by timely unloading chromatin-bound PCNA from the damaged/stalled forks, coordinates the DDR pathways to safeguard the integrity of RFs under replication stress.
Mesh Terms:
Carrier Proteins, Cell Cycle Proteins, Checkpoint Kinase 2, DNA Damage, DNA Repair, DNA Replication, Methyl Methanesulfonate, Mutation, Proliferating Cell Nuclear Antigen, Protein Serine-Threonine Kinases, Rad52 DNA Repair and Recombination Protein, Replication Protein C, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Genetics
Date: Dec. 10, 2025
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