PT  - JOURNAL ARTICLE
AU  - Chen, Guo
AU  - Xu, Ke
AU  - Xie, Maohua
AU  - Owonikoko, Taofeek K.
AU  - Ramalingam, Suresh S.
AU  - Doetsch, Paul W.
AU  - Deng, Xingming
TI  - Abstract 2757: Mcl-1 dictates DNA double-strand break repair pathway choice
AID  - 10.1158/1538-7445.AM2016-2757
DP  - 2016 Jul 15
TA  - Cancer Research
PG  - 2757--2757
VI  - 76
IP  - 14 Supplement
4099  - http://cancerres.aacrjournals.org/content/76/14_Supplement/2757.short
4100  - http://cancerres.aacrjournals.org/content/76/14_Supplement/2757.full
SO  - Cancer Res2016 Jul 15; 76
AB  - Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LADNA double-strand breaks (DSBs) are mainly repaired by homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways. The choice of pathway is a critical aspect of DSB repair that is poorly understood. We show that Mcl-1 acts as a functional switch in pathway choice between HR and NHEJ. Mcl-1 is cell cycle-regulated, with expression peaking in S/G2 phase via reduction of its ubiquitination when HR occurs. Mcl-1 depletion reduces HR and enhances NHEJ. Mcl-1 overexpression results in a net increase in HR over NHEJ. Mcl-1 promotes HR-dependent DSB repair following DNA replication stress, which contributes to maintenance of genomic integrity. Mcl-1 directly interacts with Ku via its BH1 and BH3 domains. This interaction is required for Mcl-1 to inhibit Ku-mediated NHEJ, and promote Mre11 complex-mediated DNA resection and HR-dependent DSB repair. Thus, Mcl-1, in addition to its antiapoptotic function, plays an unexpected role in directing DSB repair pathway choice by skewing the balance toward HR during cell cycle progression.Citation Format: Guo Chen, Ke Xu, Maohua Xie, Taofeek K. Owonikoko, Suresh S. Ramalingam, Paul W. Doetsch, Xingming Deng. Mcl-1 dictates DNA double-strand break repair pathway choice. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2757.