RPA1

This gene encodes the largest subunit of the heterotrimeric Replication Protein A (RPA) complex, which binds to single-stranded DNA (ssDNA), forming a nucleoprotein complex that plays an important role in DNA metabolism, being involved in DNA replication, repair, recombination, telomere maintenance, and co-ordinating the cellular response to DNA damage through activation of the ataxia telangiectasia and Rad3-related protein (ATR) kinase. The nucleoprotein complex protects the single-stranded DNA from nucleases, prevents formation of secondary structures that would interfere with repair, and co-ordinates the recruitment and departure of different genome maintenance factors. This subunit contains four oligonucleotide/oligosaccharide-binding (OB) domains, though the majority of ssDNA binding occurs in two of these domains. The heterotrimeric complex has two different modes of ssDNA binding, a low-affinity and high-affinity mode, determined by which ssDNA binding domains are utilized. The different binding modes differ in the length of DNA bound and in the proteins with which it interacts, thereby playing a role in regulating different genomic maintenance pathways. [provided by RefSeq, Sep 2017]

Replication Protein A1

As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism (PubMed:27723720, PubMed:27723717).
Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage (PubMed:9430682).
In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response (PubMed:24332808).
It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin in response to DNA damage (PubMed:17765923).
Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair (PubMed:7697716).
Also plays a role in base excision repair (BER) probably through interaction with UNG (PubMed:9765279).
Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance (PubMed:17959650).
As part of the alternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNA polymerase alpha but could support DNA synthesis by polymerase delta in presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange (PubMed:19996105).

Biological Process base-excision repairManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process cellular response to DNA damage stimulusManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process DNA recombinationManual Assertion Based On ExperimentTAS:ProtInc
Biological Process DNA repairManual Assertion Based On ExperimentIDA:ComplexPortal
Biological Process DNA replicationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process DNA unwinding involved in DNA replicationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process DNA-templated DNA replicationManual Assertion Based On ExperimentTAS:ProtInc
Biological Process double-strand break repair via homologous recombinationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process meiotic cell cycleManual Assertion Based On ExperimentIBA:GO_Central
Biological Process mismatch repairManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process nucleotide-excision repairManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein localization to chromosomeManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process telomere maintenanceManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process telomere maintenance via telomeraseManual Assertion Based On ExperimentIBA:GO_Central

Nucleus
Nucleus, PML body
Enriched in PML bodies in cells displaying alternative lengthening of their telomeres.

DNA damage-induced 'Lys-63'-linked polyubiquitination by PRPF19 mediates ATRIP recruitment to the RPA complex at sites of DNA damage and activation of ATR (PubMed:24332808).
Ubiquitinated by RFWD3 at stalled replication forks in response to DNA damage: ubiquitination by RFWD3 does not lead to degradation by the proteasome and promotes removal of the RPA complex from stalled replication forks, promoting homologous recombination (PubMed:26474068).
Sumoylated on lysine residues Lys-449 and Lys-577, with Lys-449 being the major site. Sumoylation promotes recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination. Desumoylated by SENP6.