Structural highlights
Function
PCNA1_SACS2 One of the sliding clamp subunits that acts as a moving platform for DNA processing. Responsible for tethering the catalytic subunit of DNA polymerase to DNA during high-speed replication. Heterotrimer stimulates the Holliday junction resolvase Hjc. DNA polymerase I, DNA ligase and the flap endonuclease may be constitutively associated with the PCNA heterotrimer forming a scanning complex able to couple DNA synthesis and Okazaki fragment maturation.[1] [2]
Publication Abstract from PubMed
DNA ligases act in the final step of many DNA repair pathways and are commonly regulated by the DNA sliding clamp proliferating cell nuclear antigen (PCNA), but there are limited insights into the physical basis for this regulation. Here, we use single-particle cryoelectron microscopy (cryo-EM) to analyze an archaeal DNA ligase and heterotrimeric PCNA in complex with a single-strand DNA break. The cryo-EM structures highlight a continuous DNA-binding surface formed between DNA ligase and PCNA that supports the distorted conformation of the DNA break undergoing repair and contributes to PCNA stimulation of DNA ligation. DNA ligase is conformationally flexible within the complex, with its domains fully ordered only when encircling the repaired DNA to form a stacked ring structure with PCNA. The structures highlight DNA ligase structural transitions while docked on PCNA, changes in DNA conformation during ligation, and the potential for DNA ligase domains to regulate PCNA accessibility to other repair factors.
Cryo-EM structures and biochemical insights into heterotrimeric PCNA regulation of DNA ligase.,Sverzhinsky A, Tomkinson AE, Pascal JM Structure. 2022 Mar 3;30(3):371-385.e5. doi: 10.1016/j.str.2021.11.002. Epub 2021 , Nov 26. PMID:34838188[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dionne I, Nookala RK, Jackson SP, Doherty AJ, Bell SD. A heterotrimeric PCNA in the hyperthermophilic archaeon Sulfolobus solfataricus. Mol Cell. 2003 Jan;11(1):275-82. PMID:12535540 doi:10.1016/s1097-2765(02)00824-9
- ↑ Dorazi R, Parker JL, White MF. PCNA activates the Holliday junction endonuclease Hjc. J Mol Biol. 2006 Dec 1;364(3):243-7. Epub 2006 Sep 9. PMID:17011573 doi:http://dx.doi.org/10.1016/j.jmb.2006.09.011
- ↑ Sverzhinsky A, Tomkinson AE, Pascal JM. Cryo-EM structures and biochemical insights into heterotrimeric PCNA regulation of DNA ligase. Structure. 2022 Mar 3;30(3):371-385.e5. PMID:34838188 doi:10.1016/j.str.2021.11.002
