Characterization of Mre11 Gene Variants in Cancer

Location

Jereld R. Nicholson Library: Grand Avenue

Subject Area

Biology

Description

Among the different damages that a cell can undergo, DNA double-strand break (DSB) is the most detrimental one. DNA contains all the necessary information for a cell's proper functioning and replication; therefore, a break that damages both of its strands completely destabilizes the DNA molecules. If not properly repaired, this could lead to genomic instability and tumorigenesis. Cells repair DSBs by two repair pathways — homology-directed repair (HDR) and non-homologous end-joining (NHEJ). Recently a back-up NHEJ pathway has been reported and is referred to as alternate-NHEJ (Alt-NHEJ). Although Alt-NHEJ is advantageous for damaged cells, it can mutate the DNA sequences at the junctions, which may lead to an altered genome that can have severe biological consequences. Mre11 is an essential component of the MRN complex and plays a key role in DSB repair pathways as HDR, NHEJ and Alt-NHEJ. Mre11 possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity which are essential for DNA end-processing. Recently Mre11 is shown to be overexpressed in breast cancer and high Mre11 expression was associated with a more malignant behavior in breast cancer. Furthermore, germline mutations of the Mre11 gene was identified in a recent screening of hereditary susceptibility to breast and/or ovarian cancer. Mutations in DNA repair genes can have a significant impact on cancer prognosis and treatment. We are focusing to determine whether germline and somatic mutations of Mre11 can lead to tumorigenesis and alter responses to chemotherapies.

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Characterization of Mre11 Gene Variants in Cancer

Jereld R. Nicholson Library: Grand Avenue

Among the different damages that a cell can undergo, DNA double-strand break (DSB) is the most detrimental one. DNA contains all the necessary information for a cell's proper functioning and replication; therefore, a break that damages both of its strands completely destabilizes the DNA molecules. If not properly repaired, this could lead to genomic instability and tumorigenesis. Cells repair DSBs by two repair pathways — homology-directed repair (HDR) and non-homologous end-joining (NHEJ). Recently a back-up NHEJ pathway has been reported and is referred to as alternate-NHEJ (Alt-NHEJ). Although Alt-NHEJ is advantageous for damaged cells, it can mutate the DNA sequences at the junctions, which may lead to an altered genome that can have severe biological consequences. Mre11 is an essential component of the MRN complex and plays a key role in DSB repair pathways as HDR, NHEJ and Alt-NHEJ. Mre11 possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity which are essential for DNA end-processing. Recently Mre11 is shown to be overexpressed in breast cancer and high Mre11 expression was associated with a more malignant behavior in breast cancer. Furthermore, germline mutations of the Mre11 gene was identified in a recent screening of hereditary susceptibility to breast and/or ovarian cancer. Mutations in DNA repair genes can have a significant impact on cancer prognosis and treatment. We are focusing to determine whether germline and somatic mutations of Mre11 can lead to tumorigenesis and alter responses to chemotherapies.