Double strand break metabolism and cancer susceptibility: Lessons from the Mre11 complex Journal Article
| Authors: | Petrini, J. H. J.; Theunissen, J. W. F. |
| Article Title: | Double strand break metabolism and cancer susceptibility: Lessons from the Mre11 complex |
| Abstract: | Hypomorphic mutants affecting the Mre11 complex components Mre11 (Mre11ATLD1/ATLD1) and Nbs1 (Nbs1ΔB/ΔB) have been established in the mouse. These mutations recapitulate those inherited in human chromosome fragility syndromes, the ataxia-telangiectasia like disorder and Nijmegen breakage syndrome. At the cellular level, the human and murine mutants exhibit defects in the intra S and G2/M checkpoints and marked chromosome instability. Whereas these outcomes are associated with predisposition to malignancy in humans, similar predisposition was not observed in either Mre11ATLD1/ATLD1 or Nbs1ΔB/ΔB mice. These data demonstrate that chromosome breakage per se is insufficient to significantly enhance the initiation of tumorigenesis. However, these mutations greatly enhanced the risk of malignancy in p53+/- mice. We propose that proper metabolism of chromosome breaks arising during DNA replication is uniquely important for suppressing loss of heterozygosity and thus the penetrance of recessive oncogenic lesions. |
| Keywords: | unclassified drug; dna binding protein; gene mutation; genetics; mutation; dna-binding proteins; review; nonhuman; dna replication; neoplasm; neoplasms; mitosis; mouse; animal; metabolism; animals; mice; mre11 protein; dna damage; cell cycle; cell cycle s phase; cancer susceptibility; animal model; protein; genotype; protein p53; physiology; carcinogenesis; nibrin; dna strand breakage; double stranded dna; lymphoma; dna repair enzymes; tumor suppressor protein p53; chromosomal instability; nijmegen breakage syndrome; cell cycle g2 phase; heterozygosity loss; polydeoxyribonucleotide synthase; disease predisposition; penetrance; ataxia telangiectasia; disease susceptibility; chromosome instability; recessive inheritance; mre11a protein, mouse; lymphomagenesis; chromosome fragility; humans; human; article; g2/m checkpoint; intra s phase checkpoint; mre11a protein, human; ataxia telangiectasia like disorder; dna double strand breakage; hypomorphic mutation |
| Journal Title: | Cell Cycle |
| Volume: | 3 |
| Issue: | 5 |
| ISSN: | 1538-4101 |
| Publisher: | Taylor & Francis Inc. |
| Date Published: | 2004-05-01 |
| Start Page: | 541 |
| End Page: | 542 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 15034299 |
| DOI: | 10.4161/cc.3.5.834 |
| DOI/URL: | |
| Notes: | Cell Cycle -- Cited By (since 1996):14 -- Export Date: 16 June 2014 -- Source: Scopus |
