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

• Published in: Mutagenesis Vol. 13; no. 1; pp. 57 - 60
• Main Authors: HENDERSON, D. S, GLOVER, D. M
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.01.1998
• Subjects: Animals; Biological and medical sciences; Chromosome Breakage - genetics; DNA - metabolism; DNA Damage; DNA Repair - genetics; DNA Transposable Elements - genetics; Drosophila; Drosophila - enzymology; Drosophila - genetics; Female; FEN-1 protein; Fundamental and applied biological sciences. Psychology; Male; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Mutation - genetics; p21 protein; Proliferating Cell Nuclear Antigen - genetics; Proliferating Cell Nuclear Antigen - metabolism; Transposases - physiology; Chromosomal aberration; Insecta; Drosophila; Drosophilidae; Double strand break; Chromosome break; Gene; Arthropoda; DNA; Lesion; Mutation; Invertebrata; Repair; Diptera; PCNA antigen
• ISSN: 0267-8357; 1464-3804
• DOI: 10.1093/mutage/13.1.57

Proliferating cell nuclear antigen (PCNA) has several roles in progression through S phase: it is required for the function of DNA polymerases δ and ε 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.