DNA end processing by polynucleotide kinase/phosphatase

Abstract

Scission of one or both strands of the DNA duplex occurs as ionizing radiation and oxidative DNA damage mount a constant assault our genomes. Like a broken limb, or split piece of wood, DNA strand breaks are typically not clean. That is, they lack the DNA 3′-hydroxyl and 5′-phosphate moieties needed for DNA repair synthesis by DNA polymerases and DNA end joining by DNA ligases (Fig. 1A). For instance, IR-induced DNA single-strand breaks (SSBs) or double-strand breaks (DSBs) harbor “dirty” chemically heterogeneous termini including 3′-phosphates (3′-PO4) and 5′-hydroxyl (5′-OH) DNA ends (Fig. 1A) (1). Variably adducted DNA termini also arise during the metabolism of DNA base damage by DNA glycosylases, from failed topoisomerase reactions (i.e., 3′ and 5′ topoisomerase protein adducts), and from aborted DNA ligation reactions (i.e., 5′-adenylate adducts) (2⇓–4). To cope with structurally diverse DNA termini, eukaryotic cells have acquired an extensive array of enzymatic activities to tailor DNA ends for ligation. Now, in PNAS, key molecular insights into the mechanisms of DNA end recognition and processing are emerging (5).