8COB

Crystal structure of human PCNA in complex with ERCC6L2 PIP box peptide

Summary for 8COB

• Entry DOI: 10.2210/pdb8cob/pdb
• Descriptor: Proliferating cell nuclear antigen, DNA excision repair protein ERCC-6-like 2 (3 entities in total)
• Functional Keywords: ercc6l2, rad26l, hebo, pcna, dna binding protein, centromere associated replication factor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 91087.65

Authors

Ariza, A. (deposition date: 2023-02-27, release date: 2023-04-19, Last modification date: 2024-02-07)

Primary citation

Carnie, C.J.,Armstrong, L.,Sebesta, M.,Ariza, A.,Wang, X.,Graham, E.,Zhu, K.,Ahel, D.
ERCC6L2 mitigates replication stress and promotes centromere stability.
Cell Rep, 42:112329-112329, 2023

PubMed Abstract: Structurally complex genomic regions, such as centromeres, are inherently difficult to duplicate. The mechanism behind centromere inheritance is not well understood, and one of the key questions relates to the reassembly of centromeric chromatin following DNA replication. Here, we define ERCC6L2 as a key regulator of this process. ERCC6L2 accumulates at centromeres and promotes deposition of core centromeric factors. Interestingly, ERCC6L2 cells show unrestrained replication of centromeric DNA, likely caused by the erosion of centromeric chromatin. Beyond centromeres, ERCC6L2 facilitates replication at genomic repeats and non-canonical DNA structures. Notably, ERCC6L2 interacts with the DNA-clamp PCNA through an atypical peptide, presented here in a co-crystal structure. Finally, ERCC6L2 also restricts DNA end resection, acting independently of the 53BP1-REV7-Shieldin complex. We propose a mechanistic model, which reconciles seemingly distinct functions of ERCC6L2 in DNA repair and DNA replication. These findings provide a molecular context for studies linking ERCC6L2 to human disease.

PubMed: 37014751
DOI: 10.1016/j.celrep.2023.112329

Experimental method

X-RAY DIFFRACTION (2.73 Å)