한빛사 논문
Abstract
Eunhee Choi,1,6 Pil-Gu Park,1,6 Hae-ock Lee,1,6,7 Yoo-Kyung Lee,1 Gyeong Hoon Kang,2 Jong Won Lee,3,4 Wonshik Han,3 Ho Chang Lee,2 Dong-Young Noh,3 Sergey Lekomtsev,5 and Hyunsook Lee1,*
1 Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, 599 Gwanak-Ro, Gwanak-ku, Seoul 151-742, Korea
2 Department of Pathology
3 Department of Surgery and Cancer Research Institute
Seoul National University, College of Medicine, Seoul 110-744, Korea
4 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea
5 Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK
6 These authors contributed equally to this work
7 Present address: Department of Pathology, Korea University School of Medicine, Seoul 135-710, Korea
*Correspondence: Hyunsook Lee
Summary
Germline mutations that inactivate BRCA2 promote early-onset cancer with chromosome instability. Here, we report that BRCA2 regulates the spindle assembly checkpoint (SAC). Previously, we reported that BubR1 acetylation is essential for SAC activity. In this study we show that BRCA2 recruits the PCAF acetyltransferase and aids in BubR1 acetylation during mitosis. In the absence of BRCA2, BubR1 acetylation is abolished, and the level of BubR1 decreases during mitosis. Similarly, Brca2-deficient mouse embryonic fibroblasts exhibited weak SAC activity. Transgenic mice that were engineered to have interruptions in the BRCA2-BubR1 association exhibited marked decrease of BubR1 acetylation, weakened SAC activity, and aneuploidy. These transgenic mice developed spontaneous tumors at 40% penetrance. Moreover, immunohistochemical analyses of human breast cancer specimens suggested that BRCA2 mutation and BubR1 status is closely linked. Our results provide an explanation for how mutation of BRCA2 can lead to chromosome instability without apparent mutations in SAC components.
논문정보
관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기