Licensing the first responder: PCBP1 controls PARP1 activation

Abstract

Poly(ADP-ribose) polymerase 1 (PARP1) is a key guardian of genome integrity and a major therapeutic target in cancer. Although its catalytic activation has been extensively studied, how PARP1 is restrained under physiological conditions yet rapidly mobilized following DNA damage has remained unclear. In this issue, Shu et al. (2026) identify poly(rC)-binding protein 1 (PCBP1) as an endogenous gatekeeper that restricts PARP1 access to damaged DNA. DNA double-strand breaks trigger SIRT7-dependent deacetylation of PCBP1, releasing this brake and enabling PARP1 to initiate DNA damage signaling. Beyond identifying a new regulator, this work uncovers an upstream licensing step in PARP1 activation and points to an alternative strategy for modulating PARP1 that complements conventional catalytic inhibition.

Keywords

PARP1 / PCBP1 / DNA damage response / SIRT7 / PARylation / PARP inhibitor

References

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Funding

National Natural Science Foundation of China(82273147)

Natural Science Foundation of Shenzhen Municipality(JCYJ20240813142012017)

Rights & permissions

Shenzhen University Medical School