TY - JOUR
AU - de Murcia, Gilbert
AB - 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.
TI - Functional interaction between PARP‐1 and PARP‐2 in chromosome stability and embryonic development in mouse
JF - The EMBO Journal
DO - 10.1093/emboj/cdg206
DA - 2003-05-01
UR - https://www.deepdyve.com/lp/springer-journals/functional-interaction-between-parp-1-and-parp-2-in-chromosome-3zatrFXFl9
SP - 2255
EP - 2263
VL - 22
IS - 9
DP - DeepDyve
ER -