Polη, a Y-family translesion synthesis polymerase, promotes cellular tolerance of Myc-induced replication stress. Kurashima K, Sekimoto T, Oda T, Yamashita T. (IMCR, Gunma Univ.) Kawabata T (ABDI, Nagasaki Univ.) Hanaoka F (Faculty of Science, Gakushuin Univ.)
Growth of precancerous and cancer cells relies on their tolerance of oncogene-induced replication stress (RS). Translesion synthesis (TLS) plays an essential role in cellular tolerance of various types of RS and bypasses replication barriers by employing specialized polymerases. Here, we report that Polη, a Y-family TLS polymerase, promotes cellular tolerance of Myc-induced RS. In the absence of Polη, Myc-induced DSB formation depended on MUS81-EME2 endonuclease complex, and concomitant depletion of MUS81-EME2 and Polη enhanced RS and cell death in a synergistic manner. Together, these results indicate that Polη facilitates fork progression during Myc-induced RS, thereby helping cells tolerate the resultant deleterious effects. Additionally, the present study highlights the possibility of a synthetic sick or lethal interaction between Polη and MUS81-EME2 in cells experiencing Myc-induced RS.
Polη, a Y-family translesion synthesis polymerase, promotes cellular tolerance of Myc-induced replication stress. Kurashima K, Sekimoto T, Oda T, Kawabata T, Hanaoka F, Yamashita T. J Cell Sci. 2018 May 18. doi: 10.1242/jcs.212183. [Epub ahead of print]