signature=42aca1523d1c69df9ccb3b04492633d4,A UVR-induced G2-phase checkpoint response to ssDNA gaps ...

摘要：

UVR is a major environmental risk factor for the of . Here we describe a coupled DNA-damage tolerance () mechanism and induced in response to suberythemal doses of UVR that is commonly defective in . This coupled response is triggered by a small number of UVR-induced DNA lesions incurred during that are not repaired by (). These lesions are detected during , but rather than stalling replication, they trigger the -dependent formation of (ssDNA) gaps. The ssDNA attracts A (), which initiates -(and -related/) checkpoint signaling, and colocalizes with components of the and pathways. We demonstrate that depletion of delays both the resolution of foci and exit from the arrest, indicating the involvement of -dependent in ssDNA gap repair during . Moreover, the presence of and suggests that an error-free mechanism may also contribute to repair. Loss of the UVR-induced checkpoint results in increased UVR signature mutations after exposure to suberythemal UVR. We propose that defects in the UVR-induced checkpoint and repair mechanism are likely to contribute to .

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