Lethality in PARP-1/Ku80 double mutant mice reveals physiological synergy during early embryogenesis.
作者： Melinda S. Henrie , Akihiro Kurimasa , Sandeep Burma , Josiane Ménissier-de Murcia , Gilbert de Murcia
DOI: 10.1016/S1568-7864(02)00199-4
关键词:
摘要: Ku is an abundant heterodimeric nuclear protein, consisting of 70-kDa and 86-kDa tightly associated subunits that comprise the DNA binding component DNA-dependent protein kinase. Poly(ADP)ribose polymerase-1 (PARP-1) a 113-kDa catalyzes synthesis poly(ADP-ribose) on target proteins. Both PARP-1 recognize bind to ends. functions in non-homologous end joining (NHEJ) repair pathway whereas single strand break base excision (BER) pathways. Recent studies have revealed Ku80 interact vitro. To determine whether association has any physiological significance or synergistic function vivo, mice lacking both were generated. The resulting offspring died during embryonic development displaying abnormalities around gastrulation stage. In addition, PARP-1-/-Ku80-/- cultured blastocysts had increased level apoptosis. These data suggest are essential for normal embryogenesis loss genomic integrity leading cell death through apoptosis likely cause lethality observed these mice.
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