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.
Henderson
D S
DS
Cancer Research Campaign Laboratories, University of Dundee, UK. d.s.henderson@dundee.ac.uk
Glover
D M
DM
D000818:Animals; D019457:Chromosome Breakage / Q000235:genetics*; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004251:DNA Transposable Elements / Q000235:genetics; D004330:Drosophila / Q000201:enzymology / Q000235:genetics*; D005260:Female; D008297:Male; D009154:Mutation / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics* / Q000378:metabolism; D019895:Transposases / Q000502:physiology*
D004251:DNA Transposable Elements; D018809:Proliferating Cell Nuclear Antigen; D004247:DNA; D019895:Transposases