HMCES (F2J3S) Rabbit mAb #17636

HMCES is an abasic site processing protein belonging to the SOS-response associated peptidase (SRAP) family (1,2). In DNA, loss of a base or nucleotide generates an abasic or apurinic/apyrimidinic (AP) site, one of the most common DNA lesions (1,2). HMCES plays a critical role in recognizing these abasic (AP) sites (1,2). HMCES directly binds proliferating cell nuclear antigen (PCNA) and single-stranded DNA (ssDNA) at replication forks, forming covalent cross-links to promote error-free genome repair (1-3). The HMCES DNA-protein cross-link (DPC) prevents translesion DNA synthesis and endonuclease activity, thereby stopping the generation of mutations and double-stranded DNA (dsDNA) breaks (2). Following this action, the HMCES-DPC is degraded by the proteasome or self-reversed (2,3). In dsDNA, AP sites are repaired via the base excision repair (BER) pathway (1-3).

During somatic hypermutation (SHM) in B cells, HMCES suppresses deletions within immunoglobulin (Ig) genes but allows other types of point mutations to occur, resulting in antigen-specific high-affinity antibodies (4). HMCES deficiency impairs class switch recombination (CSR) in B cells, leading to weakened antibody production (5).

In APOBEC3A-expressing tumors, disruption of HMCES may increase the tumor’s sensitivity to therapies such as ionizing radiation (IR), oxidative stress, and ATR inhibition (6).