Target intelligence / Profile preview

Replication protein A 70 kDa DNA-binding subunit (RPA1)

Target
RPA1
Molecular classification
Single-stranded DNA-binding protein, DNA replication/repair factor, Genome maintenance protein, Other (heterotrimeric complex subunit)
01

Overview

Replication protein A 70 kDa DNA-binding subunit (RPA1) is the largest subunit of the heterotrimeric replication protein A complex, a major single-stranded DNA-binding protein in eukaryotes[1][2][3]. RPA1 is essential for DNA metabolism, including DNA replication, repair (especially nucleotide excision and homologous recombination), recombination, and telomere maintenance. It binds to ssDNA regions to protect them from nucleases and secondary structure formation, mediates recruitment of repair and checkpoint factors (such as ATR/ATRIP, RAD51, RAD52, XPA, XPG), and coordinates the response to DNA damage[1][2]. Structurally, RPA1 contains multiple DNA-binding domains and serves as a hub for protein-protein interactions critical to genome integrity. Loss or mutation of RPA1 impairs DNA repair and replication, resulting in increased sensitivity to DNA-damaging agents, and clinical syndromes associated with defective genomic maintenance, such as cancer and bone marrow failure syndromes[1][2][3].

Other names
Replication protein A1RPA1RPA70Replication factor A protein 1Single-stranded DNA-binding proteinRP-A p70RF-A protein 1HSSBMST075REPA1RF-ARP-AMSTP075
02

Mechanism of action

DNA-damaging agents may act by inducing DNA lesions, where RPA1 function is essential for repair[3]. Hypothetical mechanisms for drug targeting might include inhibition of ssDNA binding, disruption of protein-protein interactions in DNA repair complexes, or modulation of DNA damage response pathways, but such drugs are not named in above sources.

03

Biological functions

DNA replicationDNA repair (nucleotide excision, homologous recombination, base excision repair)DNA recombinationTelomere maintenanceCellular response to DNA damageMaintenance of genome stabilityCell cycle checkpoint regulation
04

Disease associations

CancerPulmonary fibrosis and/or bone marrow failure syndrome, telomere-relatedDyskeratosis congenita (autosomal recessive)Other DNA repair deficiency syndromes
05

Safety considerations

Therapeutic inhibition of RPA1 could lead to genomic instabilityImpaired DNA repairCytotoxicity, particularly in proliferative tissues[2]Mutations cause hypersensitivity to DNA-damaging agents[2]Targeting may pose risk of bone marrow failureDevelopmental toxicityOff-target cell death
06

Biomarkers

Germline or somatic mutation in RPA1 may serve as biomarker for cancer risk, response to DNA-damaging therapy, and some rare genetic syndromes like dyskeratosis congenita[1][3]

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