Lethality in PARP-1/Ku80 double mutant mice reveals physiological synergy during early embryogenesis Journal Article
| Authors: | Henrie, M. S.; Kurimasa, A.; Burma, S.; Ménissier-de Murcia, J.; De Murcia, G.; Li, G. C.; Chen, D. J. |
| Article Title: | Lethality in PARP-1/Ku80 double mutant mice reveals physiological synergy during early embryogenesis |
| 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. © 2002 Elsevier Science B.V. All rights reserved. |
| Keywords: | controlled study; dna-binding proteins; nonhuman; conference paper; protein function; mouse; mouse mutant; animals; mice; cell death; dna repair; apoptosis; embryo; animal experiment; animal model; genotype; embryo development; protein interaction; genome analysis; cause of death; cell culture; data analysis; progeny; developmental disorder; protein subunit; ku antigen; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; dna helicases; embryonic lethality; lethality; blastocyst; genes, lethal; gastrulation; poly(adp-ribose) polymerases; base excision repair; embryo death; antigens, nuclear; ku80; poly(adenosine diphosphate ribose); parp-1; homologous repair; priority journal; non-programmatic; ziziphus mauritiana |
| Journal Title: | DNA Repair |
| Volume: | 2 |
| Issue: | 2 |
| ISSN: | 1568-7864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2003-02-03 |
| Start Page: | 151 |
| End Page: | 158 |
| Language: | English |
| DOI: | 10.1016/s1568-7864(02)00199-4 |
| PUBMED: | 12531386 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 25 September 2014 -- Source: Scopus |
