EndJoiningVariante

EndJoiningVariante is a proposed variant of the cellular pathway that repairs DNA double-strand breaks through end joining. Conceptually, it sits between classical non-homologous end joining (NHEJ) and alternative end joining families, arising in contexts where the canonical machinery is limited or deregulated.

Mechanistically, EndJoiningVariante is thought to initiate with binding of core end-joining sensors, then engage a distinct, context-dependent ligation complex and limited end processing. It is characterized by a defined reliance on short microhomologies and, in some cases, templated insertions. The involvement of polymerase theta or related polymerases may occur in specific cell types, but this is not universal.

Compared with classical NHEJ and MMEJ, EndJoiningVariante shows reduced dependence on Lig4 and Ku proteins and can display unique junction signatures, including modest insertions and predictable microhomology footprints. Its activity can be influenced by replication timing and chromatin state.

Biological significance is debated. In theory, EndJoiningVariante contributes to genome stability when the primary NHEJ pathway is compromised and may affect mutational outcomes in cancer or during genome editing. Its pharmacological sensitivity matrix could differ from other end-joining routes, with implications for targeted therapies.

Current discussions frame EndJoiningVariante as a proposed concept requiring further experimental validation. While several models support its existence, conclusive in vivo evidence remains limited, and cross-study consistency is an active area of investigation.