Recognition of DNA termini by the cterminal region of the Ku80 and the dnadependent protein kinase catalytic subunit

Derek S. Woods, Catherine Sears, John Turchi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

DNA double strand breaks (DSBs) can be generated by endogenous cellular processes or exogenous agents in mammalian cells. These breaks are highly variable with respect to DNA sequence and structure and all are recognized in some context by the DNA-dependent protein kinase (DNA-PK). DNA-PK is a critical component necessary for the recognition and repair of DSBs via non-homologous end joining (NHEJ). Previously studies have shown that DNA-PK responds differentially to variations in DSB structure, but how DNA-PK senses differences in DNA substrate sequence and structure is unknown. Here we explore the enzymatic mechanisms by which DNA-PK is activated by various DNA substrates and provide evidence that the DNA-PK is differentially activated by DNA structural variations as a function of the C-terminal region of Ku80. Discrimination based on terminal DNA sequence variations, on the other hand, is independent of the Ku80 C-terminal interactions and likely results exclusively from DNA-dependent protein kinase catalytic subunit interactions with the DNA. We also show that sequence differences in DNA termini can drastically influence DNA repair through altered DNA-PK activation. These results indicate that even subtle differences in DNA substrates influence DNA-PK activation and ultimately the efficiency of DSB repair.

Original languageEnglish
Article numbere0127321
JournalPLoS One
Volume10
Issue number5
DOIs
StatePublished - May 15 2015

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DNA-Activated Protein Kinase
protein subunits
protein kinases
Protein Kinases
Catalytic Domain
DNA
Repair
DNA sequences
Substrates
Chemical activation
Double-Stranded DNA Breaks
Joining
DNA Repair
Cells
nucleotide sequences

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Recognition of DNA termini by the cterminal region of the Ku80 and the dnadependent protein kinase catalytic subunit. / Woods, Derek S.; Sears, Catherine; Turchi, John.

In: PLoS One, Vol. 10, No. 5, e0127321, 15.05.2015.

Research output: Contribution to journalArticle

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