ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and facilitates DNA repair

被引:43
作者
Bleuyard, Jean-Yves [1 ]
Buisson, Remi [2 ]
Masson, Jean-Yves [2 ]
Esashi, Fumiko [1 ]
机构
[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[2] Univ Laval, Canc Res Ctr, Genome Stabil Lab, Hotel Dieu Quebec, Quebec City, PQ G1R 2J6, Canada
关键词
PALB2; chromatin association; homologous recombination; DNA repair; cancer; HOMOLOGOUS RECOMBINATION; FANCONI-ANEMIA; CANCER; BRCA2; MUTATIONS; PARTNER; BREAKS; MRG15;
D O I
10.1038/embor.2011.243
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The partner and localizer of breast cancer 2 susceptibility protein (PALB2) is crucial for the repair of DNA damage by homologous recombination. Here, we report that chromatin-association motif (ChAM), an evolutionarily conserved motif in PALB2, is necessary and sufficient to mediate its chromatin association in both unperturbed and damaged cells. ChAM is distinct from the previously described PALB2 DNA-binding regions. Deletion of ChAM decreases PALB2 and Rad51 accumulation at DNA damage sites and confers cellular hypersensitivity to the genotoxic drug mitomycin C. These results suggest that PALB2 chromatin association via ChAM facilitates PALB2 function in the cellular resistance to DNA damage.
引用
收藏
页码:135 / 141
页数:7
相关论文
共 19 条
[11]   PALB2 mutations in European familial pancreatic cancer families [J].
Slater, E. P. ;
Langer, P. ;
Niemczyk, E. ;
Strauch, K. ;
Butler, J. ;
Habbe, N. ;
Neoptolemos, J. P. ;
Greenhalf, W. ;
Bartsch, D. K. .
CLINICAL GENETICS, 2010, 78 (05) :490-494
[12]   PALB2 Regulates Recombinational Repair through Chromatin Association and Oligomerization [J].
Sy, Shirley M. -H. ;
Huen, Michael S. Y. ;
Zhu, Yongyou ;
Chen, Junjie .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (27) :18302-18310
[13]   MRG15 Is a Novel PALB2-interacting Factor Involved in Homologous Recombination [J].
Sy, Shirley M. -H. ;
Huen, Michael S. Y. ;
Chen, Junjie .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (32) :21127-21131
[14]   PALB2 is an integral component of the BRCA complex required for homologous recombination repair [J].
Sy, Shirley M. H. ;
Huen, Michael S. Y. ;
Chen, Junjie .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (17) :7155-7160
[15]   PALB2/FANCN: Recombining Cancer and Fanconi Anemia [J].
Tischkowitz, Marc ;
Xia, Bing .
CANCER RESEARCH, 2010, 70 (19) :7353-7359
[16]   Fanconi anemia is associated with a defect in the BRCA2 partner PALB2 [J].
Xia, Bing ;
Dorsman, Josephine C. ;
Ameziane, Najim ;
de Vries, Yne ;
Rooimans, Martin A. ;
Sheng, Qing ;
Pals, Gerard ;
Errami, Abdellatif ;
Gluckman, Eliane ;
Llera, Julian ;
Wang, Weidong ;
Livingston, David M. ;
Joenje, Hans ;
de Winter, Johan P. .
NATURE GENETICS, 2007, 39 (02) :159-161
[17]   Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2 [J].
Xia, Bing ;
Sheng, Qing ;
Nakanishi, Koji ;
Ohashi, Akihiro ;
Wu, Jianmin ;
Christ, Nicole ;
Liu, Xinggang ;
Jasin, Maria ;
Couch, Fergus J. ;
Livingston, David M. .
MOLECULAR CELL, 2006, 22 (06) :719-729
[18]   PALB2 Functionally Connects the Breast Cancer Susceptibility Proteins BRCA1 and BRCA2 [J].
Zhang, Fan ;
Fan, Qiang ;
Ren, Keqin ;
Andreassen, Paul R. .
MOLECULAR CANCER RESEARCH, 2009, 7 (07) :1110-1118
[19]   PALB2 Links BRCA1 and BRCA2 in the DNA-Damage Response [J].
Zhang, Feng ;
Ma, Jianglin ;
Wu, Jiaxue ;
Ye, Lin ;
Cai, Hong ;
Xia, Bing ;
Yu, Xiaochun .
CURRENT BIOLOGY, 2009, 19 (06) :524-529