Inactive PARP1 causes embryonic lethality and genome instability in a dominant-negative manner.

ABSTRACT: PARP1 (poly-ADP ribose polymerase 1) is recruited and activated by DNA strand breaks, catalyzing the generation of poly-ADP-ribose (PAR) chains from NAD+. PAR relaxes chromatin and recruits other DNA repair factors, including XRCC1 and DNA Ligase 3, to maintain genomic stability. Here we show that, in contrast to the normal development of Parp1-null mice, heterozygous expression of catalytically inactive Parp1 (E988A, Parp1^+/A) acts in a dominant-negative manner to disrupt murine embryogenesis. As such, all the surviving F1 Parp1^+/A mice are chimeras with mixed Parp1^+/AN (neoR retention) cells that act similarly to Parp1^+/-. Pure F2 Parp1^+/A embryos were found at Mendelian ratios at the E3.5 blastocys

SUBMITTER: Shao Z 

PROVIDER: S-EPMC10401025 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature