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Unique Repair Component of Breast Cancer Cell DNA Synthesome
Jen Sekowski, Ph.D.
School of Medicine, University of Maryland, Baltimore
When a breast cell proliferates, it must make a copy of its DNA to pass on to its daughter cell. We have established that the process of DNA replication is carried out by a tightly organized multiprotein complex (termed the DNA synthesome). It was previously hypothesized that a cancerous breast cell is prone to accumulate errors (mutations) in the DNA. I have recently demonstrated for the first time that the DNA synthesome isolated from breast cancer cells makes significantly more errors when it replicated DNA than the synthesome derived from non-cancer cells. Another recent and significant discovery I have made has established that the breast cell synthesome contains (in addition to all of the DNA replication proteins) DNA mismatch repair proteins (which are known to be critical for correcting mistakes in DNA). Discovery of structural and/or functional alterations in the synthesome coupled mismatch repair proteins will reveal a new molecular mechanism contributing to the increase in error-prone DNA replication exhibited in breast cancer cells. Greater understanding of the mechanism(s) underlying the increased DNA alterations and mutations in cancer cells will provide a unique opportunity t 1) develop novel biomarkers enabling earlier and more accurate diagnosis/prognosis of breast cancer, and 2) reveal new targets for improved anti-cancer therapeutics.
