The E2F transcription factor family plays a critical role in cell cycle progression and gene regulation. This study identifies new E2F target genes, revealing that E2F regulates genes involved in DNA replication, DNA repair, and cell cycle checkpoints. Using a combination of chromatin immunoprecipitation and DNA microarray analysis, researchers identified 127 genes bound by E2F4 in primary fibroblasts, including genes involved in DNA damage checkpoints, chromatin assembly, and mitotic spindle regulation. These findings indicate that E2F directly links cell cycle progression with the regulation of genes essential for DNA synthesis and surveillance. E2F1 and E2F4 bind overlapping sets of target genes, with E2F1 associated with genes involved in DNA replication and repair. The study also shows that E2F regulates genes involved in multiple cell cycle checkpoints, including the G2/M checkpoint. Furthermore, the loss of p107 and p130 leads to derepression of E2F4 target genes, highlighting the role of E2F in cell cycle regulation. The results suggest that E2F is not only involved in the G1/S transition but also in the regulation of genes required for DNA repair and checkpoint control. This study provides a comprehensive understanding of E2F's role in cell cycle regulation and DNA repair, emphasizing its importance in maintaining genomic integrity.The E2F transcription factor family plays a critical role in cell cycle progression and gene regulation. This study identifies new E2F target genes, revealing that E2F regulates genes involved in DNA replication, DNA repair, and cell cycle checkpoints. Using a combination of chromatin immunoprecipitation and DNA microarray analysis, researchers identified 127 genes bound by E2F4 in primary fibroblasts, including genes involved in DNA damage checkpoints, chromatin assembly, and mitotic spindle regulation. These findings indicate that E2F directly links cell cycle progression with the regulation of genes essential for DNA synthesis and surveillance. E2F1 and E2F4 bind overlapping sets of target genes, with E2F1 associated with genes involved in DNA replication and repair. The study also shows that E2F regulates genes involved in multiple cell cycle checkpoints, including the G2/M checkpoint. Furthermore, the loss of p107 and p130 leads to derepression of E2F4 target genes, highlighting the role of E2F in cell cycle regulation. The results suggest that E2F is not only involved in the G1/S transition but also in the regulation of genes required for DNA repair and checkpoint control. This study provides a comprehensive understanding of E2F's role in cell cycle regulation and DNA repair, emphasizing its importance in maintaining genomic integrity.