Inactive Parp2 Causes Tp53-dependent Lethal Anemia by Blocking Replication-associated Nick Ligation in Erythroblasts

Significance: This work shows that the hematological toxicities associated with PARP inhibitors stem not from impaired PARP1 or PARP2 enzymatic activity but rather from the presence of inactive PARP2 protein. Mechanistically, these toxicities reflect a unique role of PARP2 at 5'-phosphorylated DNA nicks during DNA replication in erythroblasts.