Fig. 6: Model of USP37’s role in protecting replisomes from premature disassembly.
From: USP37 prevents premature disassembly of stressed replisomes by TRAIP
In wild-type cells (WT), USP37 counteracts trans ubiquitylation by TRAIP (Supplementary Fig. 1a) when CMGs are stalled at sites of DPCs/topological stress. Thus, USP37 activity allows replisomes to eventually complete DNA synthesis and be unloaded by a termination-specific CRL2Lrr1-dependent pathway. In the absence of USP37, TRAIP hyper-ubiquitylates CMG at sites of topological stress, causing premature CMG disassembly, DNA damage, and cell death. When both USP37 and TRAIP are absent converging CMGs cannot be prematurely ubiquitylated and, thus, may ultimately terminate normally. For simplicity, the region in between two stalled replisomes is shown as plectonemes.
