The function of SMARCAL1 translocase stabilizes replication forks during replication stress

Abstract

DNA replication stress imposes a great threat to the integrity of genome SMARCAL1 and HLTF DNA translocases are recruited to stalled replication forks to promote fork reversal; therefore stabilizing forks and preventing the collapse of replication forks However whether HLTF and SMARCAL1 function redundantly or they are involved in resolving different type of DNA lesions remains unclear Here we report that SMARCAL1 plays an important role in fork stability The depletion of SMARCAL1 generates high frequency of sister chromatid exchanges (SCEs) Strikingly the single molecule DNA fibre analysis revealed that SMARCAL1 contributes to the slowing of replication progression in response to MMS-induced DNA lesions The combined depletion of SMARCAL1 and HLTF causes more sensitivity to DNA damaging agent methyl methanesulfonate (MMS) than the single depletion of each gene Furthermore SMARCAL1/HLTF double-depleted cells results in the hyperphosphorylation of RPA32 at S4/S8 sites indicating the collapse of forks Our findings reveal that SMARCAL1 and HLTF have additive effects on the maintenance of fork stability during replication stress

Date of Award	2020
Original language	English
Supervisor	Hung-Jiun Liaw (Supervisor)