Chromosome fragmentation resulting from an inability to repair transposase-induced DNA double-strand breaks in PCNA mutants of Drosophila.

Proliferating cell nuclear antigen (PCNA) has several roles in progression through S phase: it is required for the function of DNA polymerases delta and epsilon and physically associates with the structure-specific nuclease FEN-1 that is essential for Okazaki fragment processing. The cyclindependent kinase inhibitor p21 appears to displace FEN-1 from PCNA to inhibit DNA replication and possibly permit participation of PCNA in nucleotide excision repair. Here we show that PCNA is also indispensable for repair of DNA double-strand breaks (DSBs), lesions which are not corrected by excision repair processes. When PCNA-deficient Drosophila mutants are incorporated into a genetic system that induces chromosomal site-specific DSBs upon mobilization of transposable P elements they fail to undertake DSB repair. This has dominant lethal effects: DSBs are converted into chromosome breaks that can be seen at mitosis.