RT Journal Article
SR Electronic
T1 A gatekeeping function of the replicative polymerase controls pathway choice in the resolution of lesion-stalled replisomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 676486
DO 10.1101/676486
A1 Seungwoo Chang
A1 Karel Naiman
A1 Elizabeth S. Thrall
A1 James E. Kath
A1 Slobodan Jergic
A1 Nicholas Dixon
A1 Robert P. Fuchs
A1 Joseph J Loparo
YR 2019
UL http://biorxiv.org/content/early/2019/06/21/676486.abstract
AB DNA lesions stall the replisome and proper resolution of these obstructions is critical for genome stability. Replisomes can directly replicate past a lesion by error-prone translesion synthesis. Alternatively, replisomes can reprime DNA synthesis downstream of the lesion, creating a single-stranded DNA gap that is repaired primarily in an error-free, homology-directed manner. Here we demonstrate how structural changes within the bacterial replisome determine the resolution pathway of lesion-stalled replisomes. This pathway selection is controlled by a dynamic interaction between the proofreading subunit of the replicative polymerase and the processivity clamp, which sets a kinetic barrier to restrict access of TLS polymerases to the primer/template junction. Failure of TLS polymerases to overcome this barrier leads to repriming, which competes kinetically with TLS. Our results demonstrate that independent of its exonuclease activity, the proofreading subunit of the replisome acts as a gatekeeper and influences replication fidelity during the resolution of lesion-stalled replisomes.