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Lung cancer is the most common cause of cancer‐related death worldwide, accounting for 1.8 million deaths annually. Analysis of The Cancer Genome Atlas data showed that all members of the minichromosome maintenance (MCM) family (hexamers involved in DNA replication: MCM2‐MCM7) were upregulated in lung adenocarcinoma (LUAD) tissues. High expression of MCM4 (P = 0.0032), MCM5 (P = 0.0032), and MCM7 (P = 0.0110) significantly predicted 5‐year survival rates in patients with LUAD. Simurosertib (TAK‐931) significantly suppressed the proliferation of LUAD cells by inhibiting cell division cycle 7‐mediated MCM2 phosphorylation. This finding suggested that MCM2 might be a therapeutic target for LUAD. Moreover, analysis of the epigenetic regulation of MCM2 showed that miR‐139‐3p, miR‐378a‐5p, and miR‐2110 modulated MCM2 expression in LUAD cells. In patients with LUAD, understanding the role of these miRNAs may improve prognoses.

Lung cancer is the most common cause of cancer‐related death worldwide, accounting for 1.8 million deaths annually. Analysis of The Cancer Genome Atlas data showed that all members of the minichromosome maintenance (MCM) family (hexamers involved in DNA replication: MCM2‐MCM7) were upregulated in lung adenocarcinoma (LUAD) tissues. High expression of MCM4 (P = 0.0032), MCM5 (P = 0.0032), and MCM7 (P = 0.0110) significantly predicted 5‐year survival rates in patients with LUAD. Simurosertib (TAK‐931) significantly suppressed the proliferation of LUAD cells by inhibiting cell division cycle 7‐mediated MCM2 phosphorylation. This finding suggested that MCM2 might be a therapeutic target for LUAD. Moreover, analysis of the epigenetic regulation of MCM2 showed that miR‐139‐3p, miR‐378a‐5p, and miR‐2110 modulated MCM2 expression in LUAD cells. In patients with LUAD, understanding the role of these miRNAs may improve prognoses. [ABSTRACT FROM AUTHOR]

Treslin/Ticrr is required for the initiation of DNA replication and binds to MTBP (Mdm2 Binding Protein). Here, we show that in Xenopus egg extract, MTBP forms an elongated tetramer with Treslin containing two molecules of each protein. Immunodepletion and add-back experiments show that Treslin–MTBP is rate limiting for replication initiation. It is recruited onto chromatin before S phase starts and recruitment continues during S phase. We show that DDK activity both increases and strengthens the interaction of Treslin–MTBP with licensed chromatin. We also show that DDK activity cooperates with CDK activity to drive the interaction of Treslin–MTBP with TopBP1 which is a regulated crucial step in pre-initiation complex formation. These results suggest how DDK works together with CDKs to regulate Treslin–MTBP and plays a crucial in selecting which origins will undergo initiation.

Treslin/Ticrr is required for the initiation of DNA replication and binds to MTBP (Mdm2 Binding Protein). Here, we show that in Xenopus egg extract, MTBP forms an elongated tetramer with Treslin containing two molecules of each protein. Immunodepletion and add-back experiments show that Treslin-MTBP is rate limiting for replication initiation. It is recruited onto chromatin before S phase starts and recruitment continues during S phase. We show that DDK activity both increases and strengthens the interaction of Treslin-MTBP with licensed chromatin. We also show that DDK activity cooperates with CDK activity to drive the interaction of Treslin-MTBP with TopBP1 which is a regulated crucial step in pre-initiation complex formation. These results suggest how DDK works together with CDKs to regulate Treslin-MTBP and plays a crucial in selecting which origins will undergo initiation.