Structural basis of HMCES interactions with DNA reveals multivalent substrate recognition

Abstract

HMCES can covalently crosslink to abasic sites in single-stranded DNA at stalled replication forks to prevent genome instability. Here, we report crystal structures of the HMCES SRAP domain in complex with DNA-damage substrates, revealing interactions with both single-stranded and duplex segments of 3 overhang DNA. HMCES may also bind gapped DNA and 5 overhang structures to align single stranded abasic sites for crosslinking to the conserved Cys2 of its catalytic triad.