PARP-2 depletion results in lower radiation cell survival but cell line-specific differences in poly(ADP-ribose) levels.
Cell. Mol. Life Sci.. 2014-10-22; 72(8): 1585-1597
Lire sur PubMed
1. Cell Mol Life Sci. 2015 Apr;72(8):1585-97. doi: 10.1007/s00018-014-1765-2. Epub
2014 Oct 22.
PARP-2 depletion results in lower radiation cell survival but cell line-specific
differences in poly(ADP-ribose) levels.
Boudra MT(1), Bolin C, Chiker S, Fouquin A, Zaremba T, Vaslin L, Biard D,
Cordelières FP, Mégnin-Chanet F, Favaudon V, Fernet M, Pennaneach V, Hall J.
(1)Institut Curie, Centre de Recherche, Bât. 110-112, Centre Universitaire,
91405, Orsay, France.
Poly(ADP-ribose) polymerase-2 (PARP-2) activity contributes to a cells’
poly(ADP-ribosyl)ating potential and like PARP-1, has been implicated in several
DNA repair pathways including base excision repair and DNA single strand break
repair. Here the consequences of its stable depletion in HeLa, U20S, and AS3WT2
cells were examined. All three PARP-2 depleted models showed increased
sensitivity to the cell killing effects on ionizing radiation as reported in
PARP-2 depleted mouse embryonic fibroblasts providing further evidence for a role
in DNA strand break repair. The PARP-2 depleted HeLa cells also showed both
higher constitutive and DNA damage-induced levels of polymers of ADP-ribose (PAR)
associated with unchanged PARP-1 protein levels, but higher PARP activity and a
concomitant lower PARG protein levels and activity. These changes were
accompanied by a reduced maximal recruitment of PARP-1, XRCC1, PCNA, and PARG to
DNA damage sites. This PAR-associated phenotype could be reversed in HeLa cells
on re-expression of PARP-2 and was not seen in U20S and AS3WT2 cells. These
results highlight the complexity of the relationship between different members of
the PARP family on PAR metabolism and suggest that cell model dependent
phenotypes associated with the absence of PARP-2 exist within a common background
of radiation sensitivity.
PMID: 25336152 [Indexed for MEDLINE]