The Bloom syndrome protein limits the lethality associated with RAD51 deficiency.
Little is known about the functional interaction between the Bloom's syndrome protein (BLM) and the recombinase RAD51 within cells. Using RNA interference technology, we provide the first demonstration that RAD51 acts upstream from BLM to prevent anaphase bridge formation. RAD51 downregulation was associated with an increase in the frequency of BLM-positive anaphase bridges, but not of BLM-associated ultrafine bridges. Time-lapse live microscopy analysis of anaphase bridge cells revealed that BLM promoted cell survival in the absence of Rad51. Our results directly implicate BLM in limiting the lethality associated with RAD51 deficiency through the processing of anaphase bridges resulting from the RAD51 defect. These findings provide insight into the molecular basis of some cancers possibly associated with variants of the RAD51 gene family.
Lahkim Bennani-Belhaj
Kenza
K
Institut Curie, Centre de Recherche, Centre Universitaire, Orsay, France.
Rouzeau
Sébastien
S
Buhagiar-Labarchède
Géraldine
G
Chabosseau
Pauline
P
Onclercq-Delic
Rosine
R
Bayart
Emilie
E
Cordelières
Fabrice
F
Couturier
Jérôme
J
Amor-Guéret
Mounira
M
D000705:Anaphase / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D051135:Rad51 Recombinase / Q000235:genetics*; D053484:RecQ Helicases / Q000235:genetics* / Q000378:metabolism; D012854:Sister Chromatid Exchange / Q000235:genetics
D051135:Rad51 Recombinase; C097151:Bloom syndrome protein; D053484:RecQ Helicases