SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator ofchromatin, subfamily A-like1), also known as DNA-dependent ATPase A and HARP(Hep-A-related proteins), maintains genome integrity during DNA replication.SMARCAL1 has ATP-dependent annealing helicase activity, which helps tostabilise stalled replication forks and facilitate DNA repair duringreplication. Biochemically, SMARCAL1 can bind to DNA that contains single- anddouble-stranded regions such as forks and DNA hairpins. DNA binding activatesits ATPase activity, and this activity promotes DNA single-stranded annealing[, ].SMARCAL1 is a multifunctional protein. The ATPase domain, which lies in the C-terminal half of the protein, is split into two regions of primary amino acidsequence by a 115-amino-acid linker sequence. The N-terminalhalf of the protein contains a highly sequence conserved ssDNA-binding proteinreplication protein A (RPA)-binding domain, and one or two HARP domain(s). Theevolutionarily conserved HARP domain determines the annealing helicaseactivity required for the in vivo and in vitro functions of SMARCAL1 [, , ].
HARP (HepA-related protein; also known as SMARCAL1 and DNA-dependent ATPase A) is an ATP-driven annealing helicase that acts throughout the genome to re-anneal stably unwound DNA []. It helps to stabilise stalled replication forks and facilitate DNA repair during replication [, ]. SMARCAL1 binds directly to forked DNA structures or can be recruited to replication forks via interaction with the single-stranded DNA binding protein RPA []. Mutations in the HARP gene are responsible for a pleiotropic disorder known as Schimke immuno-osseous dysplasia (SIOD) [].
