Vindigni Lab Studies BRCA2-Deficient Cancer Cells

Alessandro Vindigni, Ph.D., published studies in Nature Communications on BRCA-deficient cancer cells, including why these cells are more sensitive to chemotherapy drugs and a pathway used to rescue cells after drug removal.

Many chemotherapy drugs work by inducing DNA lesions, causing replication forks and blocking replication of the cell. BRCA proteins protect these stalled replication forks from degradation. The lack of protection in BRCA-deficient cells results in an increased sensitivity to chemotherapy drugs.

The researchers also found that even after the replication forks have stalled and been degraded, the cells can use the break-induced replication (BIR) pathway to rescue the degraded forks and avoid cell death. This alternate pathway could provide a second target to sensitize BRCA-deficient cells even more to chemotherapy drugs and to prevent cells from developing resistance to chemotherapy.

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Vindigni Nat Commun Fig 6 2017-crop

Roles of BRCA2, CtIP/MRE11/EXO1 and MUS81/POLD3 in reversed fork
protection, degradation, and cleavage/restart, respectively.

Department of Biochemistry and Molecular Biology