Figure 7.

Model for THO function at telomeres. The THO complex localizes to telomeres and assists TERRA packaging into RNPs. In the absence of Thp2, telomeric R-loops accumulate and unassembled, nascent TERRA that may remain entangled around the DNA template accumulates. Failure of TERRA maturation or unscheduled TERRA expression interferes with chromosome end cap formation and protection from the telomere end-trimming enzyme Exo1, which induced telomere shortening. Upon replication stress, perturbed replication forks may collide with TERRA-entangled DNA. Enhanced telomere shortening of TERRA-entangled telomeres upon fork stalling is partially but not solely mediated by Exo1. The additional shortening may be due to enhanced telomere erosion or incomplete DNA replication of chromosome ends. R-loops are not responsible for Exo1- and replication stress-induced telomere shortening.