APOBEC3B

APOBEC3B is a human enzyme that belongs to the APOBEC3 family of cytidine deaminases. It is encoded by the APOBEC3B gene, located on chromosome 22q13.1. The enzyme acts on single-stranded DNA, catalyzing the deamination of cytosine to uracil, which can lead to mutations after DNA replication.

Mechanistically, APOBEC3B converts cytosine to uracil in exposed single-stranded DNA during processes such as DNA replication and repair. This activity can produce C-to-T transitions directly and, through error-prone repair, other mutation types. The enzyme is part of the innate immune defense and contributes to restricting viral replication by editing viral genomes or replication intermediates.

In the immune context, APOBEC3B expression is inducible by interferons and other signals of viral infection. It plays a role in restricting a range of viruses and retroelements, contributing to intrinsic antiviral defense. However, its mutagenic potential extends beyond viral DNA and can affect the host genome in somatic cells.

APOBEC3B is a major source of characteristic mutational patterns found in many cancers. Mutagenesis driven by APOBEC activity is associated with specific mutational signatures, notably SBS2 and SBS13, and with instances of kataegis. This activity can contribute to intratumoral heterogeneity and the evolution of cancer, including therapy resistance in some tumors.

Genetic variation in APOBEC3B, including germline deletions that reduce A3B expression in some populations, has been linked to cancer risk in a context-dependent manner and may shift mutational burden to other APOBEC enzymes, such as APOBEC3A. Clinically, APOBEC3B activity is studied as a potential biomarker and therapeutic target, with inhibitors under investigation but not yet approved.