RAS |
Increased origin firing |
Di Micco et al., 2006Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C, Schurra C, Garré M, Nuciforo PG, Bensimon A et al. (2006) Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444:638-642.
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Impaired fork progression |
Di Micco et al., 2006Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C, Schurra C, Garré M, Nuciforo PG, Bensimon A et al. (2006) Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444:638-642.; Maya-Mendoza et al., 2015Maya-Mendoza A, Ostrakova J, Kosar M, Hall A, Duskova P, Mistrik M, Merchut-Maya JM, Hodny Z, Bartkova J, Christensen C et al. (2015) Myc and Ras oncogenes engage different energy metabolism programs and evoke distinct patterns of oxidative and DNA replication stress. Mol Oncol 9:601-616.
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Nucleotide pool depletion |
Aird et al., 2013Aird KM, Zhang G, Li H, Tu Z, Bitler BG, Garipov A, Wu H, Wei Z, Wagner SN, Herlyn M et al. (2013) Suppression of nucleotide metabolism underlies the establishment and maintenance of oncogene-induced senescence. Cell Rep 3:1252-1265.
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Transcription-replication collision |
Kotsantis et al., 2016Kotsantis P, Silva LM, Irmscher S, Jones RM, Folkes L, Gromak N and Petermann E (2016) Increased global transcription activity as a mechanism of replication stress in cancer. Nat Commun 7:13087.
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MYC |
Disturbed origin firing |
Dominguez-Sola et al., 2007Dominguez-Sola D, Ying CY, Grandori C, Ruggiero L, Chen B, Li M, Galloway DA, Gu W, Gautier J and Dalla-Favera R (2007) Non-transcriptional control of DNA replication by c-Myc. Nature 448:445-451.; Srinivasan et al., 2013Srinivasan SV, Dominguez-Sola D, Wang LC, Hyrien O and Gautier J (2013) Cdc45 is a critical effector of Myc-dependent DNA replication stress. Cell Rep 3:1629-1639.; Macheret and Halazonetis, 2018Macheret M and Halazonetis TD (2018) Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress. Nature 555:112-116.
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Impaired fork progression |
Srinivasan et al., 2013Srinivasan SV, Dominguez-Sola D, Wang LC, Hyrien O and Gautier J (2013) Cdc45 is a critical effector of Myc-dependent DNA replication stress. Cell Rep 3:1629-1639.; Maya-Mendoza et al., 2015Maya-Mendoza A, Ostrakova J, Kosar M, Hall A, Duskova P, Mistrik M, Merchut-Maya JM, Hodny Z, Bartkova J, Christensen C et al. (2015) Myc and Ras oncogenes engage different energy metabolism programs and evoke distinct patterns of oxidative and DNA replication stress. Mol Oncol 9:601-616.
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CCNE1 |
Unusual DNA structure |
Teixeira et al., 2015Teixeira LK, Wang X, Li Y, Ekholm-Reed S, Wu X, Wang P and Reed SI (2015) Cyclin E deregulation promotes loss of specific genomic regions. Curr Biol 25:1327-1333.
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Decreased origin licensing |
Ekholm-Reed et al., 2004Ekholm-Reed S, Méndez J, Tedesco D, Zetterberg A, Stillman B and Reed SI (2004) Deregulation of cyclin E in human cells interferes with prereplication complex assembly. J Cell Biol 165:789-800.
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Disturbed origin firing |
Liberal et al., 2012Liberal V, Martinsson-Alzhén HS, Liberal J, Spruck CH, Widschwendter M, McGowan CH and Reed SI (2012) Cyclin-dependent kinase subunit (Cks) 1 or Cks2 overexpression overrides the DNA damage response barrier triggered by activated oncoproteins. Proc Natl Acad Sci U S A 109:2754-2759.; Jones et al., 2013Jones RM, Mortusewicz O, Afzal I, Lorvellec M, García P, Helleday T and Petermann E (2013) Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress. Oncogene 32:3744-3753.; Macheret and Halazonetis, 2018Macheret M and Halazonetis TD (2018) Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress. Nature 555:112-116.
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Impaired fork progression |
Bartkova et al., 2006Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, Vassiliou LV, Kolettas E, Niforou K, Zoumpourlis VC et al. (2006) Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444:633-637.—-; Bester et al., 2011Bester AC, Roniger M, Oren YS, Im MM, Sarni D, Chaoat M, Bensimon A, Zamir G, Shewach DS and Kerem B (2011) Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 145:435-446.; Costantino et al., 2014Costantino L, Sotiriou SK, Rantala JK, Magin S, Mladenov E, Helleday T, Haber JE, Iliakis G, Kallioniemi OP and Halazonetis TD (2014) Break-induced replication repair of damaged forks induces genomic duplications in human cells. Science 343:88-91.
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Replication fork reversal |
Neelsen et al., 2013Neelsen KJ, Zanini IM, Herrador R and Lopes M (2013) Oncogenes induce genotoxic stress by mitotic processing of unusual replication intermediates. J Cell Biol 200:699-708.
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Nucleotide pool depletion |
Bester et al., 2011Bester AC, Roniger M, Oren YS, Im MM, Sarni D, Chaoat M, Bensimon A, Zamir G, Shewach DS and Kerem B (2011) Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 145:435-446.
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Transcription-replication collision |
Jones et al., 2013Jones RM, Mortusewicz O, Afzal I, Lorvellec M, García P, Helleday T and Petermann E (2013) Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress. Oncogene 32:3744-3753.; Macheret and Halazonetis, 2018Macheret M and Halazonetis TD (2018) Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress. Nature 555:112-116.
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CDC6 |
Increased origin firing |
Vaziri et al., 2003Vaziri C, Saxena S, Jeon Y, Lee C, Murata K, Machida Y, Wagle N, Hwang DS and Dutta A (2003) A p53-dependent checkpoint pathway prevents rereplication. Mol Cell 11:997-1008.; Sideridou et al., 2011Sideridou M, Zakopoulou R, Evangelou K, Liontos M, Kotsinas A, Rampakakis E, Gagos S, Kahata K, Grabusic K, Gkouskou K et al. (2011) Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins. J Cell Biol 195:1123-1140.
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Transcription-replication collision |
Huang et al., 2016Huang S, Xu X, Wang G, Lu G, Xie W, Tao W, Zhang H, Jiang Q and Zhang C (2016) DNA replication initiator Cdc6 also regulates ribosomal DNA transcription initiation. J Cell Sci 129:1429-1440.; Komseli et al., 2018Komseli ES, Pateras IS, Krejsgaard T, Stawiski K, Rizou SV, Polyzos A, Roumelioti FM, Chiourea M, Mourkioti I, Paparouna E et al. (2018) A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence. BMC Genomics 19:37.
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CDC25 |
Increased origin firing |
Cangi et al., 2008Cangi MG, Piccinin S, Pecciarini L, Talarico A, Dal Cin E, Grassi S, Grizzo A, Maestro R and Doglioni C (2008) Constitutive overexpression of CDC25A in primary human mammary epithelial cells results in both defective DNA damage response and chromosomal breaks at fragile sites. Int J Cancer 123:1466-1471.
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Replication fork reversal |
Neelsen et al., 2013Neelsen KJ, Zanini IM, Herrador R and Lopes M (2013) Oncogenes induce genotoxic stress by mitotic processing of unusual replication intermediates. J Cell Biol 200:699-708.
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MDM2 |
Decreased origin firing |
Frum et al., 2014Frum RA, Singh S, Vaughan C, Mukhopadhyay ND, Grossman SR, Windle B, Deb S and Deb SP (2014) The human oncoprotein MDM2 induces replication stress eliciting early intra-S-phase checkpoint response and inhibition of DNA replication origin firing. Nucleic Acids Res 42:926-940.
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Impaired fork progression |
Klusmann et al., 2016Klusmann I, Rodewald S, Müller L, Friedrich M, Wienken M, Li Y, Schulz-Heddergott R and Dobbelstein M (2016) p53 activity results in DNA replication fork processivity. Cell Rep 17:1845-1857.
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BCL-2 |
Nucleotide pool depletion |
Xie et al., 2013Xie M, Yen Y, Owonikoko TK, Ramalingam SS, Khuri FR, Curran WJ, Doetsch PW and Deng X (2013) Bcl2 induces DNA replication stress by inhibiting ribonucleotide reductase. Cancer Res 74:212-223.
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