TRAIP plays an essential role in the dissociation of PCNA from chromatin during mitosis

Abstract

AbstractLoading PCNA onto chromatin is a pivotal step in DNA replication, cell cycle progression, and genome integrity. Conversely, unloading of PCNA from chromatin is a crucial step for the maintenance of genome stability. Cells defect of the PCNA unloader ATAD5/Elg1-RFC exhibit a high level of chromatin-bound PCNA, delayed S phase progression, abnormal association/dissociation of chromatin-bound proteins, and aberrant chromosome structures, but exhibit dissociation of PCNA from chromatin in mitosis. Here, we found that TRAIP, an E3 ubiquitin ligase, plays critical roles in the removal of PCNA from chromatin during mitosis. TRAIP-depleted cells exhibited chromatin-bound PCNA even during mitosis and delayed mitotic progression and mitotic exit. Although TRAIP-depleted cells with chromatin-bound PCNA progressed into the next G1 phase, they showed reduced levels of the replication licensing factor Cdt1 and impaired S phase entry. These results demonstrate that TRAIP functions independently of ATAD5/Elg1-RFC for the removal of PCNA from chromatin during mitosis, and is required for precise cell cycle progression from mitosis to G1 phase, as well as for pre-RC formation for faithful initiation of DNA replication.