2024年11月18日 · The ERCC1-XPF heterodimer functions as an essential endonuclease within the NER pathway, facilitating the excision of helix-distorting DNA lesions. ERCC1 serves primarily in damage recognition and repair complex assembly processes, whereas XPF provides the enzymatic activity required for excising the damaged DNA strand.

To examine the role of Ercc1-Xpf in ICL repair, we monitored the phosphorylation of histone variant H2AX (gamma-H2AX). The phosphoprotein accumulates at DSBs, forming foci that can be detected by immunostaining.

2021年9月28日 · Bai et al. show that the 3′ flap endonuclease XPF-ERCC1, together with SLX4, is required for alternative end joining (A-EJ)-mediated class switching in mouse B cells. XPF-ERCC1 removes 3′ single-strand overhangs formed after end resection and microhomology annealing. Moreover, ERCC1 promotes c-myc-IgH translocations in A-EJ.

这项研究表明，可以开发靶向 ERCC1 和 XPF 的蛋白质-蛋白质相互作用的小分子来增强烷化剂对癌细胞的作用。 由于 DNA 修复酶的作用，基于烷化剂的癌症化疗的益处是有限的，而 DNA 修复酶可以减轻这些药物诱导的损伤。 蛋白 ERCC1 和 XPF 之间的相互作用涉及核苷酸切除修复途径的两个主要组成部分。 在这里，通过使用美国国家癌症研究所多样性集和一组 DrugBank 小分子，基于可用结构的虚拟筛选确定了这种相互作用的新型抑制剂。 随后，对计算机筛选进行了 …

2006年6月10日 · To further define the molecular mechanisms involved in processing interstrand crosslinks, we monitored the formation of phosphorylated histone H2AX (γ-H2AX), which is generated in chromatin near double strand break sites, following DNA damage in normal and repair-deficient human cells.

ERCC1-XPF endonuclease is required for nucleotide excision repair (NER) of helix-distorting DNA lesions. However, mutations in ERCC1 or XPF in humans or mice cause a more severe phenotype than absence of NER, prompting a search for novel repair activities of the nuclease.

Reversible protein ubiquitylation plays important roles in various processes including DNA repair. Here, we identify the deubiquitylase USP 45 as a critical DNA repair regulator. USP 45 associates with ERCC 1, a subunit of the DNA repair endonuclease XPF – ERCC 1, via a short acidic motif outside of the USP 45 catalytic domain.

The interaction between the proteins ERCC1 and XPF involves two major components of the nucleotide excision repair pathway. Here, novel inhibitors of this interaction were identified by virtual screening based on available structures with use of the National Cancer Institute diversity set and a panel of DrugBank small molecules.

2010年7月1日 · We targeted XPF–ERCC1 complex by RNA interference and assessed the repair capacity of cisplatin intrastrand and interstrand crosslinks by ELISA and alkaline comet assay, respectively. We also assessed the repair of cisplatin-ICL-induced double-strand breaks (DSBs) by monitoring γ-H2AX focus formation.

这伴随着切除修复交叉互补1表达（ercc1）的表达降低，ercc1是核苷酸切除修复途径中的关键酶。此外，与每种治疗方案相比，二甲双胍联合顺铂的放射水平最低-诱导的rad51病灶，一种同源重组修复的必需蛋白。在存在二甲双胍的情况下，电离辐射诱导的γ-h2ax和53