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Trends Genet., Mar 13 2024, S0168-9525(24)00042-8 | https://doi.org/10.1016/j.tig.2024.02.006 PCNA cycling dynamics during DNA replication and repair in mammals

Sukhyun Kang ¹, Juyeong Yoo ^1,2, Kyungjae Myung ^1,3

¹Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea

²Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea

³Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea

Correspondence: Kyungjae Myung

Abstract

Proliferating cell nuclear antigen (PCNA) is a eukaryotic replicative DNA clamp. Furthermore, DNA-loaded PCNA functions as a molecular hub during DNA replication and repair. PCNA forms a closed homotrimeric ring that encircles the DNA, and association and dissociation of PCNA from DNA are mediated by clamp-loader complexes. PCNA must be actively released from DNA after completion of its function. If it is not released, abnormal accumulation of PCNA on chromatin will interfere with DNA metabolism. ATAD5 containing replication factor C-like complex (RLC) is a PCNA-unloading clamp-loader complex. ATAD5 deficiency causes various DNA replication and repair problems, leading to genome instability. Here, we review recent progress regarding the understanding of the action mechanisms of PCNA unloading complex in DNA replication/repair pathways.

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