Pillaire Marie-Jeanne, Bétous Rémy, Hoffmann Jean-Sébastien
Labellisée Ligue contre le Cancer 2013; INSERM Unit 1037; CNRS ERL 5294; Cancer Research Center of Toulouse; CHU Purpan; Toulouse, France; Université Paul Sabatier; University of Toulouse III; Toulouse, France.
Mol Cell Oncol. 2014 Jul 15;1(1):e29902. doi: 10.4161/mco.29902. eCollection 2014.
To ensure high cell viability and genomic stability, cells have evolved two major mechanisms to deal with the constant challenge of DNA replication fork arrest during S phase of the cell cycle: (1) induction of the ataxia telangiectasia and Rad3-related (ATR) replication checkpoint mechanism, and (2) activation of a pathway that bypasses DNA damage and DNA with abnormal structure and is mediated by translesion synthesis (TLS) Y-family DNA polymerases. This review focuses on how DNA polymerase kappa (Pol κ), one of the most highly conserved TLS DNA polymerases, is involved in each of these pathways and thereby coordinates them to choreograph the response to a stalled replication fork. We also describe how loss of Pol κ regulation, which occurs frequently in human cancers, affects genomic stability and contributes to cancer development.
为确保高细胞活力和基因组稳定性，细胞进化出两种主要机制来应对细胞周期S期DNA复制叉停滞这一持续挑战：（1）诱导共济失调毛细血管扩张症和Rad3相关蛋白（ATR）复制检查点机制，以及（2）激活一条绕过DNA损伤和异常结构DNA的途径，该途径由跨损伤合成（TLS）Y家族DNA聚合酶介导。本综述重点关注DNA聚合酶κ（Pol κ），这是最保守的TLS DNA聚合酶之一，如何参与这些途径中的每一个，并因此协调它们以编排对停滞复制叉的反应。我们还描述了Pol κ调控缺失（这在人类癌症中经常发生）如何影响基因组稳定性并促进癌症发展。
