title: Interaction of human SUV3 RNA/DNA helicase with BLM helicase; loss of the SUV3 gene results in mouse embryonic lethality.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.
authors.forename: Mandy
authors.initials: M
authors.lastname: Pereira
authors.forename: Penelope
authors.initials: P
authors.lastname: Mason
authors.forename: Roman J
authors.initials: RJ
authors.lastname: Szczesny
authors.forename: Leena
authors.initials: L
authors.lastname: Maddukuri
authors.forename: Sylwia
authors.initials: S
authors.lastname: Dziwura
authors.forename: Robert
authors.initials: R
authors.lastname: Jedrzejczak
authors.forename: Erin
authors.initials: E
authors.lastname: Paul
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wojcik
authors.forename: Lien
authors.initials: L
authors.lastname: Dybczynska
authors.forename: Barbara
authors.initials: B
authors.lastname: Tudek
authors.forename: Ewa
authors.initials: E
authors.lastname: Bartnik
authors.forename: Jan
authors.initials: J
authors.lastname: Klysik
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
authors.forename: Piotr P
authors.initials: PP
authors.lastname: Stepien
mesh_terms: 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
chemical_list: 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