Ultraviolet　radiation　(UVR)　and　ionizing　radiation　(IR)　are　common　genotoxic　stresses　that　damage　human　skin,　although　the　specific　damages　to　the　genomic　DNA　are　different.　Here,　we　show　that　in　the　mouse　glabrous　skin,　both　UVR　and　IR　induce　DNA　damage,　cell　cycle　arrest,　and　condensed　cell　nuclei.　However,　only　IR　induces　mitotic　catastrophe　(MC)　in　the　epidermis.　This　is　because　UVR　induces　a　complete　blockage　of　pRB　phosphorylation　and　cell　cycle　arrest　in　the　G1　phase,　whereas　pRB　phosphorylation　remains　positive　in　a　significant　portion　of　the　epidermal　keratinocytes　following　IR　exposure.　Furthermore,　Cyclin　B1　expression　is　significantly　downregulated　only　by　IR　but　not　UVR.　Finally,　there　are　more　MC　cells　in　the　epidermis　of　p53-/-　mice　after　IR　exposure　as　compared　to　wild-type　mice.　Our　results　suggest　that　although　both　IR　and　UVR　are　genotoxic,　they　show　distinct　impacts　on　the　cell　cycle　machinery　and　thus　damage　the　epidermal　keratinocytes　via　different　mechanisms.　©　2018　John　Wiley　&　Sons　A/S.　Published　by　John　Wiley　&　Sons　Ltd