Cell cycle and apoptosis regulator protein 2 (CCAR2)

Cell cycle and apoptosis regulator protein 2 (CCAR2), also known as DBC1 or Deleted in Breast Cancer 1, is a large, multifunctional nuclear protein that plays key roles in regulating the DNA damage response, apoptosis, cell cycle progression, chromatin organization, transcription, and metabolism[1][2][4]. CCAR2 functions as an epigenetic modulator by inhibiting deacetylases such as SIRT1 and HDAC3, and a methyltransferase (SUV39H1)[2][3], thereby influencing p53-dependent apoptosis and chromatin structure. It is also a downstream effector of the Shieldin complex in the non-homologous end joining (NHEJ) pathway, restricting DNA end-resection and inhibiting homologous recombination repair[1]. CCAR2 loss in BRCA1-deficient cells promotes resistance to PARP inhibitors and crosslinking agents, an effect that is epistatic with other Shieldin factors[1]. Its activity and post-translational modifications are tightly regulated, and alterations in its function have implications in tumor development, chemosensitivity, and potentially other diseases[2][4].

Other names

Cell cycle and apoptosis regulator 2DBC1KIAA1967DBIRD complex subunit KIAA1967Deleted in breast cancer gene 1 proteinNET35p30 DBCdeleted in breast cancer 1

Inhibition of SIRT1 deacetylase activates p53-dependent apoptosis. Regulation of double-strand break repair pathway choice between homologous recombination and non-homologous end joining. Modulation of chromatin structure by inhibiting epigenetic modifiers (SIRT1, HDAC3, SUV39H1).