| First Author | León-Ortiz AM | Year | 2018 |
| Journal | Mol Cell | Volume | 69 |
| Issue | 2 | Pages | 292-305.e6 |
| PubMed ID | 29351848 | Mgi Jnum | J:257566 |
| Mgi Id | MGI:6115110 | Doi | 10.1016/j.molcel.2017.12.014 |
| Citation | Leon-Ortiz AM, et al. (2018) A Distinct Class of Genome Rearrangements Driven by Heterologous Recombination. Mol Cell 69(2):292-305.e6 |
| abstractText | Erroneous DNA repair by heterologous recombination (Ht-REC) is a potential threat to genome stability, but evidence supporting its prevalence is lacking. Here we demonstrate that recombination is possible between heterologous sequences and that it is a source of chromosomal alterations in mitotic and meiotic cells. Mechanistically, we find that the RTEL1 and HIM-6/BLM helicases and the BRCA1 homolog BRC-1 counteract Ht-REC in Caenorhabditis elegans, whereas mismatch repair does not. Instead, MSH-2/6 drives Ht-REC events in rtel-1 and brc-1 mutants and excessive crossovers in rtel-1 mutant meioses. Loss of vertebrate Rtel1 also causes a variety of unusually large and complex structural variations, including chromothripsis, breakage-fusion-bridge events, and tandem duplications with distant intra-chromosomal insertions, whose structure are consistent with a role for RTEL1 in preventing Ht-REC during break-induced replication. Our data establish Ht-REC as an unappreciated source of genome instability that underpins a novel class of complex genome rearrangements that likely arise during replication stress. |
