DNA Repair Review

Sam and Patty wrote a great review article highlighting the recent Science paper out of Dr. Jonathan Alder’s lab. For precursor lesions to progress to metastatic melanoma, it is believed that multiple mutations must occur to help the cell escape telomere crisis, deter telomere shortening, and confer immortality. The first such “hit” is usually a mutation in the TERT promoter. Pattra Chun-un, a PhD candidate in the Alder lab, identified the “2nd hit” - variants in the promotor of TPP1, similar to the mutational signatures of UV-induced DNA damage. This results in an upregulation of TPP1 expression which coincides with the upregulation of telomerase to lengthen telomeres, promoting immortalization of melanoma cells, and driving the cancer.

Find the review in DNA Repair here.

Model for melanoma development and progression in the context of UV-induced mutagenesis.

S.L. Sanford and P.L. Opresko