Role of DNA polymerase κ in the maintenance of genomic stability.
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.
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.
Marie-Jeanne
MJ
Pillaire
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.
Rémy
R
Bétous
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.
Jean-Sébastien
JS
Hoffmann
DNA polymerase κ; genetic instability; replication checkpoint; replication stress; translesion synthesis