AI Article Synopsis
- There are three types of PCNA clamp-loading complexes in humans: RFC and CTF18-RFC load PCNA onto DNA, while ATAD5-RFC exclusively unloads it.
- The study reveals that ATAD5 has two unique loops that stabilize the structure, preventing changes necessary for DNA binding, which is why it functions only as a PCNA unloader.
- Additionally, the research shows ATAD5-RFC can open a gap in the PCNA structure at a different location than previously known, expanding our understanding of how PCNA dynamics work.
Article Abstract
Humans have three different proliferating cell nuclear antigen (PCNA) clamp-loading complexes: RFC and CTF18-RFC load PCNA onto DNA, but ATAD5-RFC can only unload PCNA from DNA. The underlying structural basis of ATAD5-RFC unloading is unknown. We show here that ATAD5 has two unique locking loops that appear to tie the complex into a rigid structure, and together with a domain that plugs the DNA-binding chamber, prevent conformation changes required for DNA binding, likely explaining why ATAD5-RFC is exclusively a PCNA unloader. These features are conserved in the yeast PCNA unloader Elg1-RFC. We observe intermediates in which PCNA bound to ATAD5-RFC exists as a closed planar ring, a cracked spiral or a gapped spiral. Surprisingly, ATAD5-RFC can open a PCNA gap between PCNA protomers 2 and 3, different from the PCNA protomers 1 and 3 gap observed in all previously characterized clamp loaders.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563871 | PMC |
| http://dx.doi.org/10.1038/s41594-024-01332-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The human ATAD5 has evolved unique structural elements to function exclusively as a PCNA unloader.
Nat Struct Mol Biol
November 2024
Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.
Article Synopsis
- There are three types of PCNA clamp-loading complexes in humans: RFC and CTF18-RFC load PCNA onto DNA, while ATAD5-RFC exclusively unloads it.
- The study reveals that ATAD5 has two unique loops that stabilize the structure, preventing changes necessary for DNA binding, which is why it functions only as a PCNA unloader.
- Additionally, the research shows ATAD5-RFC can open a gap in the PCNA structure at a different location than previously known, expanding our understanding of how PCNA dynamics work.
PCNA Unloading Is Crucial for the Bypass of DNA Lesions Using Homologous Recombination.
Int J Mol Sci
March 2024
The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
DNA Damage Tolerance (DDT) mechanisms allow cells to bypass lesions in the DNA during replication. This allows the cells to progress normally through the cell cycle in the face of abnormalities in their DNA. PCNA, a homotrimeric sliding clamp complex, plays a central role in the coordination of various processes during DNA replication, including the choice of mechanism used during DNA damage bypass.
View Article and Find Full Text PDFStructure of the PCNA unloader Elg1-RFC.
Sci Adv
March 2024
DNA Replication Laboratory and Howard Hughes Medical Institute, The Rockefeller University, NY, New York, USA.
During DNA replication, the proliferating cell nuclear antigen (PCNA) clamps are loaded onto primed sites for each Okazaki fragment synthesis by the AAA heteropentamer replication factor C (RFC). PCNA encircling duplex DNA is quite stable and is removed from DNA by the dedicated clamp unloader Elg1-RFC. Here, we show the cryo-EM structure of Elg1-RFC in various states with PCNA.
View Article and Find Full Text PDFThe Atad5 RFC-like complex is the major unloader of proliferating cell nuclear antigen in Xenopus egg extracts.
J Biol Chem
January 2024
Faculty of Science, Kyushu University, Fukuoka, Japan. Electronic address:
Proliferating cell nuclear antigen (PCNA) is a homo-trimeric clamp complex that serves as the molecular hub for various DNA transactions, including DNA synthesis and post-replicative mismatch repair. Its timely loading and unloading are critical for genome stability. PCNA loading is catalyzed by Replication factor C (RFC) and the Ctf18 RFC-like complex (Ctf18-RLC), and its unloading is catalyzed by Atad5/Elg1-RLC.
View Article and Find Full Text PDFControl of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader.
Elife
August 2023
The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Telomeres cap and protect the linear eukaryotic chromosomes. Telomere length is determined by an equilibrium between positive and negative regulators of telomerase activity. A systematic screen for yeast mutants that affect telomere length maintenance in the yeast revealed that mutations in any of ~500 genes affects telomere length.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!