Publication Date:
2013-12-07
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047655/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047655/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- R01 GM076020/GM/NIGMS NIH HHS/ -- R37 GM020056/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 3;343(6166):88-91. doi: 10.1126/science.1243211. Epub 2013 Dec 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Geneva, 1205 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24310611" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Cycle
;
Cyclin E/biosynthesis/genetics
;
*DNA Breaks, Double-Stranded
;
DNA Polymerase III/genetics/*physiology
;
DNA Repair/*genetics
;
DNA Replication/*genetics
;
*Gene Duplication
;
Humans
;
Neoplasms/*genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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