Restriction of replication fork regression activities by a conserved SMC complex
Molecular Cell , Volume 56 - Issue 3 p. 436- 445
Conserved, multitasking DNA helicases mediate diverse DNA transactions and are relevant for human disease pathogenesis. These helicases and their regulation help maintain genome stability during DNA replication and repair. We show that the structural maintenance of chromosome complex Smc5-Smc6 restrains the replication fork regression activity of Mph1 helicase, but not its D loop disruptive activity. This regulatory mechanism enables flexibility in replication fork repair without interfering with DNA break repair. Invitro studies find that Smc5-Smc6 binds to a Mph1 region required for efficient fork regression, preventing assembly of Mph1 oligomers at the junction of DNA forks. Invivo impairment of this regulatorymechanism compensates for the inactivation of another fork regression helicase and increases reliance on joint DNA structure removal or avoidance. Our findings provide molecular insights into replication fork repair regulation and uncover a role of Smc5-Smc6 in directing Mph1 activity toward a specific biochemical outcome.
|Organisation||Department of Radiation Oncology|
Xue, X, Choi, K, Bonner, J, Chiba, T, Kwon, Y, Xu, Y, … Sung, P. (2014). Restriction of replication fork regression activities by a conserved SMC complex. Molecular Cell, 56(3), 436–445. doi:10.1016/j.molcel.2014.09.013