Fig 7. Proposed model of Mus81 involvement at budding yeast telomeres.

(A) Telomere sequence and structure presents unique challenges to replication including (i) nucleic acid structures (e.g. t-loop, telomere RNA:DNA complexes), (ii) G-quadruplex structures, (iii) telomere-binding proteins and (iv) yet unknown sources of blockage. (B) Possible mechanisms to rescue stalled replication forks. Rrm3 is a 5’-to-3’ DNA helicase required for normal replication fork progression through ‘hard to replicate’ sequences’ including telomere and subtelomeric regions by directly removing barriers [66, 109]. A second mechanism envisions the regression of the stalled fork into chicken foot that is equivalent to a Holiday junction [110]. Thirdly, Mus81-Mms4 can cleave stalled forks and potentially lead to the formation of a substrate for recombination-mediated repair and restart [110].