No Damaged Daddies

Abstract

Development Cells have evolved mechanisms to protect against damaged DNA, including the induction of apoptotic cell death. Such protection is especially important in germline cells in order to ensure the evolutionary stability of a species. The p53 homolog, p63, functions to protect the female germ line by promoting apoptosis of oocytes with damaged DNA. Beyer et al. sought to determine whether p63 also functions in the male germ line and identified p63 isoforms that are expressed in the human testis. Male germ cell-associated transcriptionally active p63 (GTAp63) is encoded by the p63 gene with a long terminal repeat (LTR), the result of an integration event of the endogenous retrovirus ERV9 LTR, inserted upstream. Spermatogenic precursors, but not mature spermatozoa, expressed GTAp63, which induced the expression of proapoptotic genes upon DNA damage. Analysis of primate DNA showed conservation of the LTR insertion in great apes and humans, which suggests that the insertion occurred recently in evolution. Besides ensuring germline genomic integrity, p63 may also act as a tumor suppressor: Examination of tissue from human testicular cancers revealed a loss of p63 expression. Proc. Natl. Acad. Sci. U.S.A. 108 , 10.1073/pnas.1016201108 (2011).