Error-prone DNA replication and repair may lead to mutations and cancer in individuals who inherit a mutant copy of the BRCA1 gene, according to a new study by Weill Cornell Medicine investigators. The discovery has potential implications for preventing the development of cancer in patients with these mutations.
The study, published Sept. 12 in Molecular Cell, provides new insights into why individuals who inherit a mutation in one copy of the BRCA1 gene often develop mutations in their remaining normal copy of the BRCA1 gene, setting the stage for tumors to develop. When these individuals’ cells are under stress, replication of the normal BRCA1 gene stalls because of the highly repetitive DNA sequences in the gene that create physical barriers to machinery that copies DNA. To fix the stall, an error-prone DNA repair mechanism kicks in.
"We have identified some of the first steps in cancer development in people carrying inherited BRCA1 mutations," said the study's senior author Dr. Jeannine Gerhardt, assistant professor of stem cell biology in obstetrics and gynecology and assistant professor of stem cell biology in reproductive medicine at the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine at Weill Cornell Medicine.
