Target intelligence / Profile preview

Homologous recombination factor with OB-fold (HROB)

Target
HROB
Molecular classification
Other (DNA repair protein, OB-fold protein, DNA binding protein)
01

Overview

Homologous recombination factor with OB-fold (HROB), also known as MCM8-9-interacting protein (MCM8IP) and C17orf53, is a DNA repair protein characterized by an oligonucleotide/oligosaccharide-binding (OB) fold. HROB binds single-stranded DNA and interacts with the recombination helicase complex MCM8-MCM9, recruiting and stimulating their activity at sites of DNA damage. It functions in the homologous recombination pathway, primarily promoting repair of DNA double-strand breaks and interstrand cross-links downstream of RAD51 loading, facilitating repair-associated DNA synthesis and replication fork restart. HROB deficiency causes hypersensitivity to crosslinking agents and PARP inhibition, defects in cell proliferation, and gametogenesis failure, implicating it as a critical player in genomic stability and tumor suppression.

Other names
MCM8-9-interacting proteinMCM8IPC17orf53MGC3130ODG11Uncharacterized protein C17orf53Homologous recombination OB-fold protein
02

Mechanism of action

Not directly targeted by drugs; however, cells lacking HROB show increased sensitivity to DNA cross-linking agents and PARP inhibitors due to impaired homologous recombination. Thus, inhibition of HROB could in principle enhance the efficacy of DNA-damaging chemotherapies or PARP inhibitors.

03

Biological functions

DNA repair (specifically repair of interstrand cross-links and double-strand breaks)Homologous recombinationRecruitment and regulation of helicase complexes (promotes MCM8-MCM9 helicase loading and activity)DNA synthesis during repairReplication fork progression and stabilityCell proliferation
04

Disease associations

Cancer (genomic instability and tumor suppression)Infertility (defective gametogenesis, including meiotic arrest and germ cell depletion)Other (primary ovarian insufficiency has been linked to interacting partners; possible broader roles in DNA repair-defective syndromes)
05

Safety considerations

Loss of HROB impairs DNA repair, leading to genomic instability and increased risk of cancer or infertility; thus, inhibition of HROB could exacerbate these risks.
06

Interacting drugs

None directly identified by name; loss of HROB sensitizes cells to DNA crosslinking agents (cisplatin, mitomycin C, psoralen+UVA), PARP inhibitors, and etoposide, but there are no known direct drug modulators reported in current literature.
07

Biomarkers

None established for patient selection or monitoring, but loss-of-function or altered expression of HROB may potentially serve as a biomarker of homologous recombination deficiency (HRD).

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