Deregulated expression of Cdc6 in the skin facilitates papilloma formation and affects the hair growth cycle

• Published in: Cell cycle (Georgetown, Tex.) Vol. 14; no. 24; pp. 3897 - 3907
• Main Authors: Búa, Sabela, Sotiropoulou, Peggy, Sgarlata, Cecilia, Borlado, Luis R, Eguren, Manuel, Domínguez, Orlando, Ortega, Sagrario, Malumbres, Marcos, Blanpain, Cedric, Méndez, Juan
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-01-2015
• Subjects: Animals; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; DNA Fragmentation; DNA Replication - genetics; DNA Replication - physiology; Female; Hair - metabolism; Hair Follicle - cytology; Hair Follicle - metabolism; Immunohistochemistry; Mice; Mice, Transgenic; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Papilloma - genetics; Papilloma - metabolism; Wound Healing - genetics; Wound Healing - physiology; hair follicle; DNA replication; Cdc6; mouse model; papilloma
• ISSN: 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2015.1120919

Cdc6 encodes a key protein for DNA replication, responsible for the recruitment of the MCM helicase to replication origins during the G1 phase of the cell division cycle. The oncogenic potential of deregulated Cdc6 expression has been inferred from cellular studies, but no mouse models have been described to study its effects in mammalian tissues. Here we report the generation of K5-Cdc6, a transgenic mouse strain in which Cdc6 expression is deregulated in tissues with stratified epithelia. Higher levels of CDC6 protein enhanced the loading of MCM complexes to DNA in epidermal keratinocytes, without affecting their proliferation rate or inducing DNA damage. While Cdc6 overexpression did not promote skin tumors, it facilitated the formation of papillomas in cooperation with mutagenic agents such as DMBA. In addition, the elevated levels of CDC6 protein in the skin extended the resting stage of the hair growth cycle, leading to better fur preservation in older mice.