SCAI, or Suppressor of Cancer Cell Invasion, is a highly conserved protein among vertebrates that has been implicated in transcriptional regulation . It lacks annotated domains and shares little sequence homology with other proteins . Research has shown that SCAI plays a significant role in DNA double-strand break (DSB) repair, response to UV-induced replicative stress, and error-free repair of DNA interstrand crosslinks (ICLs) .
SCAI promotes DNA double-strand break repair through both non-homologous end-joining (NHEJ) and homologous recombination (HR) pathways, which are essential for maintaining genome integrity after DNA damage .
DSB Repair: SCAI is enriched at DSB sites through 53BP1-dependent recruitment to DSB-surrounding chromatin and 53BP1-independent accumulation at resected DSBs . Cells lacking SCAI show reduced DSB repair capacity, increased sensitivity to DSB-inflicting agents, and genome instability . SCAI facilitates ATM kinase signaling at DSBs in repressive chromatin environments, acting as a mediator of 53BP1-dependent repair of heterochromatin-associated DSBs .
UV-Induced Replicative Stress Response: SCAI functions as a regulator of the replicative stress response caused by UV exposure . Cells with SCAI knocked down or knocked out exhibit elevated RPA-ssDNA post-UV, suggesting its involvement in the response to replicative stress . SCAI colocalizes with stalled replication forks, and its depletion promotes nascent DNA degradation. SCAI inhibits EXO1 activity on a single-stranded DNA gap in vitro, indicating its role in preventing excessive DNA resection .
ICL Repair: SCAI plays a critical role in ICL repair via the FA pathway . Mass spectrometry analysis has identified interactions between SCAI and Fanconi Anemia (FA) proteins, as well as transcription and chromatin remodeling factors. SCAI interacts with all five subunits of the polymerase ζ (Polζ) complex (REV1, REV3, REV7, POLD2, and POLD3) .
SCAI was initially identified as a suppressor of cancer cell invasion . High SCAI expression is associated with papillary thyroid cancer cells .