Interaction of human SUV3 RNA/DNA helicase with BLM helicase; loss of the SUV3 gene results in mouse embryonic lethality.
The SUV3 gene is present in all eukaryotes and encodes an RNA/DNA helicase which operates both in mitochondria and cell nuclei. To assess its function in mammals we generated a mouse mutant strain in which the 3' part of the SUV3 gene is disrupted. The mutated allele is a hypomorph transmitted from one generation to another at a frequency about 35% lower than expected while mice homozygous for the mutation die in utero before midgestation. Using ELISA binding assays we show that human SUV3 protein interacts with human WRN and BLM helicases. The binding to BLM protein was 10-fold stronger (with a K(d) of 0.5nM) than to WRN protein (K(d) of 5nM). Silencing of the SUV3 gene in the human cell line HeLa resulted in elevation of homologous recombination as measured by the frequency of sister chromatid exchange during mitotic cell division. These results indicate that the SUV3 protein is required in mammalian development and in somatic cells participates in genome maintenance through interaction with other genome fidelity housekeepers.
Pereira
Mandy
M
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.
Mason
Penelope
P
Szczesny
Roman J
RJ
Maddukuri
Leena
L
Dziwura
Sylwia
S
Jedrzejczak
Robert
R
Paul
Erin
E
Wojcik
Andrzej
A
Dybczynska
Lien
L
Tudek
Barbara
B
Bartnik
Ewa
E
Klysik
Jan
J
Bohr
Vilhelm A
VA
Stepien
Piotr P
PP
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D020964:Embryo Loss / Q000235:genetics* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D005090:Exodeoxyribonucleases; D020868:Gene Silencing; D005865:Gestational Age; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics*; D008969:Molecular Sequence Data; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D053484:RecQ Helicases / Q000378:metabolism; D012854:Sister Chromatid Exchange; D014162:Transfection; D000071657:Werner Syndrome Helicase
D034741:RNA, Small Interfering; D005090:Exodeoxyribonucleases; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; C469673:SUPV3L1 protein, human; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D053487:DEAD-box RNA Helicases