Sotirios K. Sotiriou
Broad Institute
Publications 10
#1Sotirios K. Sotiriou (Broad Institute)H-Index: 7
#2Thanos D. Halazonetis (University of Geneva)H-Index: 51
DNA replication stress is prevalent in human cancers, but absent in normal cells, suggesting that proteins involved in the cellular response to DNA replication stress could be potential therapeutic targets. SMARCAL1 and ZRANB3 are annealing helicases that mediate the repair of collapsed DNA replication forks. In a study in this issue of Cancer Research, Puccetti and colleagues report that mice lacking either SMARCAL1 or ZRANB3 activity have delayed development of MYC-induced B-cell lymphomas. Th...
1 CitationsSource
#1Natalia Lugli (University of Geneva)H-Index: 5
#2Sotirios K. Sotiriou (University of Geneva)H-Index: 7
Last.Thanos D. Halazonetis (University of Geneva)H-Index: 51
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Abstract SMARCAL1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A-Like 1), also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. Mutations in this gene are the cause of Schimke immune-osseous dysplasia (SIOD), an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions. In this review, we summarize the main roles of SMARCAL1 in DNA repair, telomere maintenance a...
7 CitationsSource
#1Natalia Lugli (University of Geneva)H-Index: 5
#2Vasilis S. Dionellis (University of Geneva)H-Index: 1
Last.Thanos D. Halazonetis (University of Geneva)H-Index: 51
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Summary The most prevalent single-nucleotide substitution (SNS) found in cancers is a C-to-T substitution in the CpG motif. It has been proposed that many of these SNSs arise during organismal aging, prior to transformation of a normal cell into a precancerous/cancer cell. Here, we isolated single intestinal crypts derived from normal tissue or from adenomas of Apc min/+ mice, expanded them minimally in vitro as organoids, and performed exome sequencing to identify point mutations that had been ...
9 CitationsSource
#1Fani-Marlen Roumelioti (Academy of Athens)H-Index: 4
#2Sotirios K. Sotiriou (University of Geneva)H-Index: 7
Last.Sarantis Gagos (Academy of Athens)H-Index: 16
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Human malignancies overcome replicative senescence either by activating the reverse‐transcriptase telomerase or by utilizing a homologous recombination‐based mechanism, referred to as alternative lengthening of telomeres (ALT). In budding yeast, ALT exhibits features of break‐induced replication (BIR), a repair pathway for one‐ended DNA double‐strand breaks (DSBs) that requires the non‐essential subunit Pol32 of DNA polymerase delta and leads to conservative DNA replication. Here, we examined wh...
44 CitationsSource
#1Sotirios K. Sotiriou (University of Geneva)H-Index: 7
#2Irene Kamileri (University of Geneva)H-Index: 4
Last.Thanos D. Halazonetis (University of Geneva)H-Index: 51
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Summary Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52 , a gene dispensable for normal development in mice, was among the top hits. In cells in which fork coll...
82 CitationsSource
#1Matilde MurgaH-Index: 24
#2Emilio LeconaH-Index: 10
Last.Oscar Fernandez-Capetillo (KI: Karolinska Institutet)H-Index: 45
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Summary The Pold3 gene encodes a subunit of the Polδ DNA polymerase complex. Pold3 orthologs are not essential in Saccharomyces cerevisiae or chicken DT40 cells, but the Schizosaccharomyces pombe ortholog is essential. POLD3 also has a specialized role in the repair of broken replication forks, suggesting that POLD3 activity could be particularly relevant for cancer cells enduring high levels of DNA replication stress. We report here that POLD3 is essential for mouse development and is also requ...
18 CitationsSource
#1Lorenzo Costantino (University of Geneva)H-Index: 2
#2Sotirios K. Sotiriou (University of Geneva)H-Index: 7
Last.Thanos D. Halazonetis (University of Geneva)H-Index: 51
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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. Segment...
219 CitationsSource
#1E. DimitriadisH-Index: 4
Last.N. PandisH-Index: 4
view all 11 authors...
19 Citations
#1Sergey I. NikolaevH-Index: 23
Last.Thanos D. HalazonetisH-Index: 51
view all 13 authors...
Oncogene-induced DNA replication stress is thought to drive genomic instability in cancer. In particular, replication stress can explain the high prevalence of focal genomic deletions mapping within very large genes in human tumors. However, the origin of single-nucleotide substitutions (SNS) in nonfamilial cancers is strongly debated. Some argue that cancers have a mutator phenotype, whereas others argue that the normal DNA replication error rates are sufficient to explain the number of observe...
40 CitationsSource
#1T. KalogeropoulosH-Index: 2
#2E. DimitriadisH-Index: 4
Last.A. ThanosH-Index: 1
view all 9 authors...