Distinct Motifs in ATAD5 C-Terminal Domain Modulate PCNA Unloading Process

Eunjin Ryu; Na Young Ha; Woojae Jung; Juyeong Yoo; Kyungjae Myung; Sukhyun Kang

doi:10.3390/cells11111832

Distinct Motifs in ATAD5 C-Terminal Domain Modulate PCNA Unloading Process

Cells. 2022 Jun 3;11(11):1832. doi: 10.3390/cells11111832.

Authors

Eunjin Ryu^{1

2}, Na Young Ha¹, Woojae Jung^{1

2}, Juyeong Yoo^{1

2}, Kyungjae Myung^{1

3}, Sukhyun Kang¹

Affiliations

¹ Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Korea.
² Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea.
³ Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea.

Abstract

Proliferating cell nuclear antigen (PCNA) is a DNA clamp that functions in key roles for DNA replication and repair. After the completion of DNA synthesis, PCNA should be unloaded from DNA in a timely way. The ATAD5-RFC-Like Complex (ATAD5-RLC) unloads PCNA from DNA. However, the mechanism of the PCNA-unloading process remains unclear. In this study, we determined the minimal PCNA-unloading domain (ULD) of ATAD5. We identified several motifs in the ATAD5 ULD that are essential in the PCNA-unloading process. The C-terminus of ULD is required for the stable association of RFC2-5 for active RLC formation. The N-terminus of ULD participates in the opening of the PCNA ring. ATAD5-RLC was more robustly bound to open-liable PCNA compared to the wild type. These results suggest that distinct motifs of the ATAD5 ULD participate in each step of the PCNA-unloading process.

Keywords: ATAD5; PCNA; PCNA unloading; RFC; RFC-like complex; RLC; SUMOylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA / metabolism
DNA Damage
DNA Replication*
DNA-Binding Proteins* / metabolism
Proliferating Cell Nuclear Antigen / metabolism

Substances

DNA-Binding Proteins
Proliferating Cell Nuclear Antigen
DNA

Grants and funding

Eunjin Ryu was supported by the Global PhD Fellowship (NRF-2017H1A2A1044961). This research was mainly supported by the Institute for Basic Science (IBS-R022-D1). This work was also partially supported by the UNIST research fund (1.180063).