Details

Autor(en) / Beteiligte

• de Murcia, Gilbert
• Ménissier de Murcia, Josiane
• Ricoul, Michelle
• Tartier, Laurence
• Niedergang, Claude
• Huber, Aline
• Dantzer, Françoise
• Schreiber, Valérie
• Amé, Jean-Christophe
• Dierich, Andrée
• LeMeur, Marianne
• Sabatier, Laure
• Chambon, Pierre

Titel

Functional interaction between PARP-1 and PARP-2 in chromosome stability and embryonic development in mouse

Ist Teil von

• The EMBO journal, 2003-05, Vol.22 (9), p.2255-2263

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2003

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• The DNA damage‐dependent poly(ADP‐ribose) polymerases, PARP‐1 and PARP‐2, homo‐ and heterodimerize and are both involved in the base excision repair (BER) pathway. Here, we report that mice carrying a targeted disruption of the PARP‐2 gene are sensitive to ionizing radiation. Following alkylating agent treatment, parp‐2−/−‐derived mouse embryonic fibroblasts exhibit increased post‐replicative genomic instability, G2/M accumulation and chromosome mis‐segregation accompanying kinetochore defects. Moreover, parp‐1−/−parp‐2−/− double mutant mice are not viable and die at the onset of gastrulation, demonstrating that the expression of both PARP‐1 and PARP‐2 and/or DNA‐dependent poly(ADP‐ribosyl) ation is essential during early embryogenesis. Interestingly, specific female embryonic lethality is observed in parp‐1+/−parp‐2−/− mutants at E9.5. Meta phase analyses of E8.5 embryonic fibroblasts highlight a specific instability of the X chromosome in those females, but not in males. Together, these results support the notion that PARP‐1 and PARP‐2 possess both overlapping and non‐redundant functions in the maintenance of genomic stability.