dorsal/arxiv
View SchemaThe Importance of DNA Repair in Tumor Suppression
| Authors | Yisroel Brumer, Eugene I. Shakhnovich |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0403018 |
| URL | https://arxiv.org/abs/q-bio/0403018 |
| DOI | 10.1103/PhysRevE.70.061912 |
Abstract
The transition from a normal to cancerous cell requires a number of highly specific mutations that affect cell cycle regulation, apoptosis, differentiation, and many other cell functions. One hallmark of cancerous genomes is genomic instability, with mutation rates far greater than those of normal cells. In microsatellite instability (MIN tumors), these are often caused by damage to mismatch repair genes, allowing further mutation of the genome and tumor progression. These mutation rates may lie near the error catastrophe found in the quasispecies model of adaptive RNA genomes, suggesting that further increasing mutation rates will destroy cancerous genomes. However, recent results have demonstrated that DNA genomes exhibit an error threshold at mutation rates far lower than their conservative counterparts. Furthermore, while the maximum viable mutation rate in conservative systems increases indefinitely with increasing master sequence fitness, the semiconservative threshold plateaus at a relatively low value. This implies a paradox, wherein inaccessible mutation rates are found in viable tumor cells. In this paper, we address this paradox, demonstrating an isomorphism between the conservatively replicating (RNA) quasispecies model and the semiconservative (DNA) model with post-methylation DNA repair mechanisms impaired. Thus, as DNA repair becomes inactivated, the maximum viable mutation rate increases smoothly to that of a conservatively replicating system on a transformed landscape, with an upper bound that is dependent on replication rates. We postulate that inactivation of post-methylation repair mechanisms are fundamental to the progression of a tumor cell and hence these mechanisms act as a method for prevention and destruction of cancerous genomes.
{
"annotation_id": "cf3ef45f-39c8-493b-a918-4d5bddc9e839",
"date_created": "2026-03-02T18:01:31.670000Z",
"date_modified": "2026-03-02T18:01:31.670000Z",
"file_hash": "e939e3d55e8635e451a6ee2b05fc5accff5e4ada22640b385debf3e1dfe7f8e1",
"private": false,
"record": {
"abstract": "The transition from a normal to cancerous cell requires a number of highly\nspecific mutations that affect cell cycle regulation, apoptosis,\ndifferentiation, and many other cell functions. One hallmark of cancerous\ngenomes is genomic instability, with mutation rates far greater than those of\nnormal cells. In microsatellite instability (MIN tumors), these are often\ncaused by damage to mismatch repair genes, allowing further mutation of the\ngenome and tumor progression. These mutation rates may lie near the error\ncatastrophe found in the quasispecies model of adaptive RNA genomes, suggesting\nthat further increasing mutation rates will destroy cancerous genomes. However,\nrecent results have demonstrated that DNA genomes exhibit an error threshold at\nmutation rates far lower than their conservative counterparts. Furthermore,\nwhile the maximum viable mutation rate in conservative systems increases\nindefinitely with increasing master sequence fitness, the semiconservative\nthreshold plateaus at a relatively low value. This implies a paradox, wherein\ninaccessible mutation rates are found in viable tumor cells. In this paper, we\naddress this paradox, demonstrating an isomorphism between the conservatively\nreplicating (RNA) quasispecies model and the semiconservative (DNA) model with\npost-methylation DNA repair mechanisms impaired. Thus, as DNA repair becomes\ninactivated, the maximum viable mutation rate increases smoothly to that of a\nconservatively replicating system on a transformed landscape, with an upper\nbound that is dependent on replication rates. We postulate that inactivation of\npost-methylation repair mechanisms are fundamental to the progression of a\ntumor cell and hence these mechanisms act as a method for prevention and\ndestruction of cancerous genomes.",
"arxiv_id": "q-bio/0403018",
"authors": [
"Yisroel Brumer",
"Eugene I. Shakhnovich"
],
"categories": [
"q-bio.GN",
"cond-mat.other",
"q-bio.OT"
],
"doi": "10.1103/PhysRevE.70.061912",
"title": "The Importance of DNA Repair in Tumor Suppression",
"url": "https://arxiv.org/abs/q-bio/0403018"
},
"schema_id": "dorsal/arxiv",
"source": {
"execution_id": "298122c9-ceb7-4aa9-a870-48de82754508",
"id": "arXiv Dataset IDs",
"type": "Model",
"variant": "snapshot-2026-03-01",
"version": "0.1.0"
},
"user_id": 1000002
}