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Literature summary for 3.6.4.B7 extracted from

  • Mason, J.M.; Dusad, K.; Wright, W.D.; Grubb, J.; Budke, B.; Heyer, W.D.; Connell, P.P.; Weichselbaum, R.R.; Bishop, D.K.
    RAD54 family translocases counter genotoxic effects of RAD51 in human tumor cells (2015), Nucleic Acids Res., 43, 3180-3196 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
recombinant overexpression in S33 cells, RAD51 fibers appear to be excluded from nucleoli, overexpression of RAD51 can cause accumulation of RAD51 foci at sites that do not contain ss-DNA Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
Homo sapiens 5739
-
additional information RAD51 fibers appear to be excluded from nucleoli in overexpressing cells Homo sapiens
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + H2O Homo sapiens
-
ADP + phosphate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q06609
-
-

Source Tissue

Source Tissue Comment Organism Textmining
fibrosarcoma cell
-
Homo sapiens
-
HT-1080 cell
-
Homo sapiens
-
MCF-7 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O
-
Homo sapiens ADP + phosphate
-
?

Synonyms

Synonyms Comment Organism
DNA repair protein RAD51 homolog 1 UniProt Homo sapiens
Rad51
-
Homo sapiens

General Information

General Information Comment Organism
malfunction translocase depletion in tumor cell lines leads to the accumulation of RAD51 on chromosomes, forming complexes that are not associated with markers of DNA damage. Combined depletion of RAD54L and RAD54B and/or artificial induction of RAD51 overexpression blocks replication and promotes chromosome segregation defects. Induction of nondamage-associated RAD51 foci is associated with reduced cell growth. Replication defects and mitotic defects associated with accumulation of nondamage-associated RAD51 complexes, overview Homo sapiens
metabolism RAD54 family translocases prevent accumulation of nondamage-associated RAD51 complexes in MCF-7 cells Homo sapiens
additional information RAD51 fibers may be helical nucleoprotein filaments Homo sapiens
physiological function the strand exchange protein RAD51 functions to promote genome stability by repairing DNA double strand breaks (DSB) and damaged replication forks. RAD51 repairs damage by forming helical nucleoprotein filaments on tracts of ssDNA. Such tracts form by 5'-3' processing of DNA ends formed by DSBs, and also as a consequence of replication fork collapse or blockage. The ssDNA-specific binding protein RPA binds rapidly and with high specificity to ssDNA tracts and, with the help of mediator proteins, promotes the recruitment of RAD51. Following nucleoprotein filament formation, RAD51 carries out a search for homologous dsDNA sequences and then promotes invasion of target duplex leading to the exchange of DNA strands that forms heteroduplex DNA within an intermediate called the displacement loop (D-loop). The ssDNA strand displaced from the target duplex during heteroduplex DNA formation also binds RPA. Subsequent stages of the recombination process result in repair of damage without loss or rearrangement of DNA sequences. RAD54L and RAD54B counteract genome-destabilizing effects of direct binding of RAD51 to dsDNA in human tumor cells. Thus, in addition to having genome-stabilizing DNA repair activity, human RAD51 has genome-destabilizing activity when expressed at high levels, as is the case in many human tumors. Within the RPA-positive subpopulation, induction of RAD51 overexpression was associated with redistribution of RPA from the diffuse staining pattern to punctate foci, suggesting that they form on undamage dsDNA, with subsequent local accumulation of RPA foci as a consequence of replisome collisions with preformed RAD51 fibers Homo sapiens