RecBCD (Exonuclease V) is inhibited by DNA adducts produced by cisplatin and ultraviolet light

Journal Article · Mon Jan 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.11.060· OSTI ID:23134072

Leung, Wai Y.; Chung, Long H.; Kava, Hieronimus W.; Murray, Vincent ^[1]

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1. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, 2052 (Australia)

Highlights: • DNA adducts inhibited the recombinational repair enzyme RecBCD. • UV-induced DNA adducts inhibited RecBCD. • Cisplatin-induced DNA adducts inhibited RecBCD. The presence of adducts on the DNA double-helix can have major consequences for the efficient functioning of DNA repair enzymes. E. coli RecBCD (exonuclease V) is involved in recombinational repair of double-strand breaks that are caused by defective DNA replication, DNA damaging agents and other factors. The holoenzyme possesses a bipolar helicase activity which helps unwind DNA from both 3′- and 5′-directions and is coupled with a potent exonuclease activity that is also capable of digesting DNA from both 3′- and 5′-ends. In this study, DNA sequences were damaged with cisplatin or UV followed by RecBCD treatment. DNA damaging agents such as cisplatin and UV induce the formation of intrastrand adducts in the DNA template. It was demonstrated that RecBCD degradation was inhibited by either cisplatin-damaged or UV-damaged DNA sequences. This is the first occasion that RecBCD has been demonstrated to be inhibited by DNA adducts induced by cisplatin or UV. In addition, we quantified the amounts of DNA remaining after RecBCD treatment and observed that the level of inhibition was concentration and dose dependent. A DNA-targeted 9-aminoacridinecarboxamide cisplatin analogue was also found to inhibit RecBCD activity.

• OSTI ID: 23134072
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 495; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
DNA ADDUCTS
DNA REPAIR
DNA REPLICATION
ENZYMES
STRAND BREAKS