期刊
JOURNAL OF FUNGI
卷 8, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/jof8060621
关键词
PCNA; DNA damage tolerance; DNA replication stress; fungal genome stability; DNA replication forks; post-translational modifications; translesion synthesis; template switch; salvage recombination
资金
- Ministerio de Ciencia, Innovacion y Universidades [PGC2018-097796-B-100]
- AGAUR-Generalitat de Catalunya [2017-SGR-569]
- CERCA Programme/Generalitat de Catalunya
- Ministerio de Ciencia y Innovacioon [PRE2019-090744]
The sliding clamp PCNA plays a crucial role in DNA replication and is involved in DNA damage tolerance and repair mechanisms through translation modifications. The ubiquitination and sumoylation of PCNA have significant effects on the nervous system and fungal pathogens.
The sliding clamp PCNA is a multifunctional homotrimer mainly linked to DNA replication. During this process, cells must ensure an accurate and complete genome replication when constantly challenged by the presence of DNA lesions. Post-translational modifications of PCNA play a crucial role in channeling DNA damage tolerance (DDT) and repair mechanisms to bypass unrepaired lesions and promote optimal fork replication restart. PCNA ubiquitination processes trigger the following two main DDT sub-pathways: Rad6/Rad18-dependent PCNA monoubiquitination and Ubc13-Mms2/Rad5-mediated PCNA polyubiquitination, promoting error-prone translation synthesis (TLS) or error-free template switch (TS) pathways, respectively. However, the fork protection mechanism leading to TS during fork reversal is still poorly understood. In contrast, PCNA sumoylation impedes the homologous recombination (HR)-mediated salvage recombination (SR) repair pathway. Focusing on Saccharomyces cerevisiae budding yeast, we summarized PCNA related-DDT and repair mechanisms that coordinately sustain genome stability and cell survival. In addition, we compared PCNA sequences from various fungal pathogens, considering recent advances in structural features. Importantly, the identification of PCNA epitopes may lead to potential fungal targets for antifungal drug development.
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