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  • Title: Lethality in PARP-1/Ku80 double mutant mice reveals physiological synergy during early embryogenesis.
    Author: Henrie MS, Kurimasa A, Burma S, Ménissier-de Murcia J, de Murcia G, Li GC, Chen DJ.
    Journal: DNA Repair (Amst); 2003 Feb 03; 2(2):151-8. PubMed ID: 12531386.
    Abstract:
    Ku is an abundant heterodimeric nuclear protein, consisting of 70- and 86-kDa tightly associated subunits that comprise the DNA binding component of DNA-dependent protein kinase. Poly(ADP-ribose) polymerase-1 (PARP-1) is a 113-kDa protein that catalyzes the synthesis of poly(ADP-ribose) on target proteins. Both Ku and PARP-1 recognize and bind to DNA ends. Ku functions in the non-homologous end joining (NHEJ) repair pathway whereas PARP-1 functions in the single strand break repair and base excision repair (BER) pathways. Recent studies have revealed that PARP-1 and Ku80 interact in vitro. To determine whether the association of PARP-1 and Ku80 has any physiological significance or synergistic function in vivo, mice lacking both PARP-1 and Ku80 were generated. The resulting offspring died during embryonic development displaying abnormalities around the gastrulation stage. In addition, PARP-1-/-/Ku80-/- cultured blastocysts had an increased level of apoptosis. These data suggest that the functions of both Ku80 and PARP-1 are essential for normal embryogenesis and that a loss of genomic integrity leading to cell death through apoptosis is likely the cause of the embryonic lethality observed in these mice.
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