Details

Autor(en) / Beteiligte

• Costantino, Lorenzo
• Sotiriou, Sotirios K.
• Rantala, Juha K.
• Magin, Simon
• Mladenov, Emil
• Helleday, Thomas
• Haber, James E.
• Iliakis, George
• Kallioniemi, Olli P.
• Halazonetis, Thanos D.

Titel

Break-Induced Replication Repair of Damaged Forks Induces Genomic Duplications in Human Cells

Ist Teil von

• Science (American Association for the Advancement of Science), 2014-01, Vol.343 (6166), p.88-91

Ort / Verlag

United States: American Association for the Advancement of Science

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• In budding yeast, one-ended DNA double-strand breaks (DSBs) and damaged replication forks are repaired by break-induced replication (BIR), a homologous recombination pathway that requires the Pol32 subunit of DNA polymerase delta. DNA replication stress is prevalent in cancer, but BIR has not been characterized in mammals. In a cyclin E overexpression model of DNA replication stress, POLD3, the human ortholog of POL32, was required for cell cycle progression and processive DNA synthesis. Segmental genomic duplications induced by cyclin E overexpression were also dependent on POLD3, as were BIR-mediated recombination events captured with a specialized DSB repair assay. We propose that BIR repairs damaged replication forks in mammals, accounting for the high frequency of genomic duplications in human cancers.