Essential Role for XRCC1 and PARP1 in the Repair of Genotoxic Damage During Spermatogenesis.

Abstract

X-ray repair cross-complementing protein 1 (XRCC1) protects cells from the effects of genotoxic stress by coordinating base excision repair (BER) and DNA single-strand break repair. XRCC1 phosphorylation and recruitment to sites of DNA damage are dependent on poly(ADP-ribose) polymerase-1 (PARP1) activity. As a central scaffolding protein, XRCC1 interacts with multiple components of BER pathway and also contributes to DNA double-strand break repair through the alternative nonhomologous end-joining pathway. In this regard, both established and recent studies have highlighted its critical role in spermatogenesis, extending beyond its classical association with PARP1. By integrating expression profiles with functional evidence, this review summarizes current insights into XRCC1 expression and subnuclear localization in spermatogenic cells, as well as its cooperative interaction with PARP1 in maintaining genomic integrity through efficient recombination and repair of genotoxic damage.