DBF4B

DBF4B is a protein-coding gene that encodes a regulatory subunit of the CDC7-like kinase complex. It is considered a paralog of DBF4 and is present in vertebrates, where it partners with the catalytic subunit CDC7 to form an active kinase complex.

The CDC7-DBF4B complex plays a key role in initiating DNA replication. By phosphorylating components of the pre-replication complex, including the MCM2-7 helicase, the complex promotes origin firing and helps drive cells from G1 into S phase. This regulatory activity contributes to the timely and orderly initiation of DNA synthesis across the genome.

Gene structure and expression patterns suggest that DBF4B produces multiple transcript variants through alternative splicing, potentially encoding one or more protein isoforms. The encoded protein is predicted to be nuclear and to contain motifs that mediate interaction with CDC7, enabling proper regulation of kinase activity. Expression of DBF4B is generally linked to cell cycle status, with higher levels observed in proliferating cells and tissue types, and in some cancer cell lines.

Biological and clinical relevance: DBF4B is thought to contribute specificity to CDC7 activity, influencing origin selection and replication timing. Experimental perturbation of DBF4B can impair origin firing and cell proliferation in certain cellular contexts, indicating its importance for normal cell cycle progression. In cancer research, altered DBF4B expression has been reported in various tumors, and the CDC7-DBF4B axis is a target of interest for therapeutic development. Small-molecule inhibitors targeting CDC7 show anti-proliferative effects in preclinical models, highlighting the potential relevance of DBF4B in disease contexts.