Familial Retinoblastoma

A 22-month-old girl presents with leukocoria and intermittent esotropia of the right eye. Her mother had bilateral retinoblastoma treated in infancy, suggesting autosomal dominant inheritance. Imaging reveals bilateral multifocal retinal masses with intralesional calcification. Germline genetic testing confirms a heterozygous loss-of-function mutation in the RB1 gene. The karyotype shown in the diagram marked **B** indicates the chromosomal locus of this mutation. According to the Knudson two-hit hypothesis, which of the following best describes the molecular mechanism by which loss of RB1 function leads to uncontrolled retinal cell proliferation?