UniProt: O43543 (XRCC2_HUMAN), 280 aa. HGNC:12829. Gene on chr7.
RecName: DNA repair protein XRCC2 (X-ray repair cross-complementing protein 2).
Also known as FANCU (Fanconi anemia complementation group U).
SIMILARITY: RecA family, RAD51 subfamily. P-loop NTPase fold; Rad51_C domain (Pfam PF08423 Rad51; InterPro IPR030547 XRCC2, IPR020588 RecA_ATP-bd).
XRCC2 is one of five human RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3).
It is an obligate structural subunit of the BCDX2 complex (RAD51B-RAD51C-RAD51D-XRCC2),
one of the two RAD51-paralog complexes (the other being CX3 = RAD51C-XRCC3).
BCDX2 acts as an HR mediator: it promotes the nucleation and extension of the RAD51
nucleoprotein filament on ssDNA. The 2023 cryo-EM structure/function paper is definitive:
PMID:37344587
PMID:37344587
PMID:37344587
PMID:37344587
RAD51C-RAD51D-XRCC2 within BCDX2 structurally mimic three RAD51 protomers aligned within a
nucleoprotein filament; RAD51B is dynamic. The ATP hydrolysis that drives the high-affinity
ssDNA-binding state is contributed by RAD51B and RAD51C, NOT by XRCC2. XRCC2 does bind
ATP (near-identical Walker A/B arrangement) but XRCC2's own catalytic function (and its
lysine finger K261) is not established as catalytic:
=> XRCC2's core role is HR mediator / RAD51 filament assembly factor, NOT a classic
recombinase/strand-exchange enzyme in its own right. This is why "ATP-dependent DNA damage
sensor activity" (InterPro IEA) is an over-annotation for XRCC2.
PMID:23149936
BCDX2 and CX3 act at different HR stages; both epistatic with BRCA2.
PMID:20207730 (Holliday junctions and replication forks; ring-shaped complexes). Supports four-way junction DNA binding (contributes_to) and replication-fork localization.
PMID:11834724 — purified Xrcc2*Rad51D subcomplex catalyzes homologous pairing; forms multimeric rings without DNA and filaments with ssDNA. Supports DNA strand invasion (involved_in).
PMID:32669601 — sequential role of RAD51 paralog complexes in fork remodeling/restart. Supports replication fork localization/function.
PMID:10422536 maintaining chromosome stability (XRCC2/XRCC3); irs1 (XRCC2-mutant) hamster cells hypersensitive to cross-linkers (MMC), genomic instability. Supports DNA repair (IGI).
PMID:9628903 in meiosis — supports meiotic cell cycle (non-core) and DNA repair (TAS).
PMID:21276791 recombinase RAD51, co-localize with the centrosome; XRCC2-deficient cells show centrosome disruption and mitotic catastrophe.
PMID:21276791 — supports centrosome localization, centrosome cycle, mitotic cell cycle (all non-core/secondary; likely indirect consequence of genome-instability, not a distinct molecular function).
Direct partner: RAD51D (O75771, NbExp=42), RAD51C (O43502). Many GO:0005515 "protein binding"
IPI annotations point to RAD51D/RAD51C (the biologically meaningful ones) plus high-throughput
interactome partners (MEOX2 P50222, etc.). "protein binding" is uninformative as a core MF ->
mark over-annotated; the meaningful content (BCDX2 assembly, RAD51D interaction) is captured by
the GO:0033063 complex annotations.
Core = BCDX2 subunit acting as RAD51-filament-assembly mediator in HR / ICL repair / replication
fork protection. Non-core/secondary = centrosome, mitotic cell cycle, meiotic cell cycle.
Over-annotations = protein binding (GO:0005515), ATP-dependent DNA damage sensor activity (GO:0140664).