Recql5 and Blm RecQ DNA helicases have nonredundant roles in suppressing crossovers.
In eukaryotes, crossovers in mitotic cells can have deleterious consequences and therefore must be suppressed. Mutations in BLM give rise to Bloom syndrome, a disease that is characterized by an elevated rate of crossovers and increased cancer susceptibility. However, simple eukaryotes such as Saccharomyces cerevisiae have multiple pathways for suppressing crossovers, suggesting that mammals also have multiple pathways for controlling crossovers in their mitotic cells. We show here that in mouse embryonic stem (ES) cells, mutations in either the Bloom syndrome homologue (Blm) or the Recql5 genes result in a significant increase in the frequency of sister chromatid exchange (SCE), whereas deleting both Blm and Recql5 lead to an even higher frequency of SCE. These data indicate that Blm and Recql5 have nonredundant roles in suppressing crossovers in mouse ES cells. Furthermore, we show that mouse embryonic fibroblasts derived from Recql5 knockout mice also exhibit a significantly increased frequency of SCE compared with the corresponding wild-type control. Thus, this study identifies a previously unknown Recql5-dependent, Blm-independent pathway for suppressing crossovers during mitosis in mice.
Hu
Yiduo
Y
Department of Genetics, Case Western Reserve University, BRB, 7th floor, 10900 Euclid Ave., Cleveland, OH 44106, USA.
Lu
Xincheng
X
Barnes
Ellen
E
Yan
Min
M
Lou
Hua
H
Luo
Guangbin
G
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001816:Bloom Syndrome / Q000235:genetics*; D003434:Crossing Over, Genetic / Q000235:genetics* / Q000502:physiology / Q000528:radiation effects; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000528:radiation effects; D005720:Gamma Rays; D017353:Gene Deletion; D020868:Gene Silencing; D018390:Gene Targeting; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D053484:RecQ Helicases; D012854:Sister Chromatid Exchange / Q000235:genetics* / Q000502:physiology; D013234:Stem Cells / Q000528:radiation effects
D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; C501069:Recql5 protein, mouse