High impact information on Ercc4

• Our observations have implications for the mechanism of gene targeting in mammalian cells and define a new role for Ercc1-Xpf in mammalian homologous recombination [1].
• The structure-specific endonuclease Ercc1-Xpf is required for targeted gene replacement in embryonic stem cells [1].
• MMC triggered sister chromatid exchanges in wild-type cells but chromatid fusions in Ercc1(-/-) and Xpf mutant cells, indicating that in their absence, repair of DSBs is prevented [2].
• To examine the role of Ercc1-Xpf in ICL repair, we monitored the phosphorylation of histone variant H2AX (gamma-H2AX) [2].
• Characterization of the mouse Xpf DNA repair gene and differential expression during spermatogenesis [3].

Biological context of Ercc4

• Ercc1 is essential for nucleotide excision repair (NER) but, unlike other NER proteins, Ercc1 and Xpf are also involved in recombination repair pathways [4].
• To investigate a possible link between mammalian XPF and recombination that occurs during meiosis, we isolated, characterized, and determined an expression profile for the mouse Xpf gene [3].
• Sequence analysis of the 38.3-kb Xpf gene, localized to a region in proximal mouse chromosome 16, revealed greater than 72% identity to human XPF in 16 regions [3].

Anatomical context of Ercc4

• Xpf transcript and protein levels were specifically elevated in adult mouse testis [3].

Other interactions of Ercc4

• However, genetic data implicate the Ercc1-Xpf endonuclease and proteins required for homologous recombination-mediated double-strand break (DSB) repair [2].

Analytical, diagnostic and therapeutic context of Ercc4

• Surprisingly, the role of Ercc1-Xpf in gene targeting is distinct from its previously identified role in removing nonhomologous termini from recombination intermediates because it was required irrespective of whether the ends of the DNA targeting constructs were heterologous or homologous to the genomic locus [1].

References