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Overexpression of RAD51 suppresses recombination defects: a possible mechanism to reverse genomic instability
| Content Provider | Oxford Academic |
|---|---|
| Author | Schild, David Wiese, Claudia |
| Copyright Year | 2010 |
| Abstract | RAD51, a key protein in the homologous recombinational DNA repair (HRR) pathway, is the major strand-transferase required for mitotic recombination. An important early step in HRR is the formation of single-stranded DNA (ss-DNA) coated by RPA (a ss-DNA-binding protein). Displacement of RPA by RAD51 is highly regulated and facilitated by a number of different proteins known as the 'recombination mediators'. To assist these recombination mediators, a second group of proteins also is required and we are defining these proteins here as 'recombination co-mediators'. Defects in either recombination mediators or co-mediators, including BRCA1 and BRCA2, lead to impaired HRR that can genetically be complemented for (i.e. suppressed) by overexpression of RAD51. Defects in HRR have long been known to contribute to genomic instability leading to tumor development. Since genomic instability also slows cell growth, precancerous cells presumably require genomic re-stabilization to gain a growth advantage. RAD51 is overexpressed in many tumors, and therefore, we hypothesize that the complementing ability of elevated levels of RAD51 in tumors with initial HRR defects limits genomic instability during carcinogenic progression. Of particular interest, this model may also help explain the high frequency of TP53 mutations in human cancers, since wild-type p53 represses RAD51 expression. |
| Related Links | https://academic.oup.com/nar/article-pdf/38/4/1061/11219152/gkp1063.pdf |
| Ending Page | 1070 |
| Starting Page | 1061 |
| File Format | |
| ISSN | 03051048 |
| e-ISSN | 13624962 |
| DOI | 10.1093/nar/gkp1063 |
| Journal | Nucleic Acids Research |
| Issue Number | 4 |
| Volume Number | 38 |
| Language | English |
| Publisher | Oxford Academic |
| Publisher Date | 2010-03-01 |
| Access Restriction | Open |
| Subject Keyword | Science and Mathematics Mutation Cancer Recombination, Genetic Neoplasms Protein Overexpression Genomic Instability Protein P53 Tp53 Gene Brca1 Gene Brca2 Gene Brca2 Protein Dna Homologous Recombinational Dna Repair |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics |
