Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability

Article Article scientifique Article Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability eng 2017 author Pilyugin Maxim 126064 author Andre Pierre-Alain 745001 author Ratajska Magdalena author Kuzniacka Alina author Limon Janusz author Tournier Benjamin 705309 author Colas Julien 844025 author Laurent Geoff author Irminger Irmgard 27662 9339-9353 10.18632/oncotarget.14068 28030839 1949-2553 Previous reports have shown that expression of BARD1δ, a deletion-bearing isoform of BARD1, correlates with tumor aggressiveness and progression. We show that expression of BARD1δ induces cell cycle arrest in vitro and in vivo in non-malignant cells. We investigated the mechanism that leads to proliferation arrest and found that BARD1δ overexpression induced mitotic arrest with chromosome and telomere aberrations in cell cultures, in transgenic mice, and in cells from human breast and ovarian cancer patients with BARD1 mutations. BARD1δ binds more efficiently than BARD1 to telomere binding proteins and causes their depletion from telomeres, leading to telomere and chromosomal instability. While this induces cell cycle arrest, cancer cells lacking G2/M checkpoint controls might continue to proliferate despite the BARD1δ-induced chromosomal instability. These features of BARD1δ may make it a genome permutator and a driver of continuous uncontrolled proliferation of cancer cells. Dewey 616.89 Dewey 618 58 Département de pédiatrie, gynécologie et obstétrique 223 60 Département de psychiatrie 225 false 1221 Neuroimagerie moléculaire en psychiatrie 983 Oncotarget 8 6 7203e606-b58f-4352-929f-f038021fdc0f Article (Published version) Public 14068-209973-3-PB.pdf 5407544 application/pdf CC BY openAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability	Oncotarget			2017	649	164

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Pilyugin, Maxim