MRG15 binds directly to PALB2 and stimulates homology-directed repair of chromosomal breaks

被引:68
作者
Hayakawa, Tomohiro [1 ]
Zhang, Fan [3 ]
Hayakawa, Noriyo [1 ]
Ohtani, Yasuko [1 ]
Shinmyozu, Kaori [2 ]
Nakayama, Jun-ichi [1 ]
Andreassen, Paul R. [3 ]
机构
[1] RIKEN, Lab Chromatin Dynam, Ctr Dev Biol, Kobe, Hyogo 6500047, Japan
[2] RIKEN, Prote Support Unit, Ctr Dev Biol, Kobe, Hyogo 6500047, Japan
[3] Univ Cincinnati, Div Expt Hematol & Canc Biol, Cincinnati Childrens Res Fdn, Dept Pediat,Coll Med, Cincinnati, OH 45229 USA
关键词
MRG15; PALB2; BRCA1; BRCA2; DNA repair; HISTONE ACETYLTRANSFERASE COMPLEX; SISTER-CHROMATID EXCHANGES; DNA-REPAIR; BRCA2; RECOMBINATION; COMPONENT; CELLS; METHYLATION; PROTEINS; PARTNER;
D O I
10.1242/jcs.060178
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
PALB2 physically and functionally connects the proteins encoded by the BRCA1 and BRCA2 breast and ovarian cancer genes into a DNA-damage-response network. However, it remains unclear how these proteins associate with chromatin that contains damaged DNA. We show here that PALB2 binds directly to a conserved chromodomain protein, MRG15, which is a component of histone acetyltransferase-deacetylase complexes. This interaction was identified by analysis of purified MRG15- and PALB2-containing protein complexes. Furthermore, MRG15 interacts with the entire BRCA complex, which contains BRCA1, PALB2, BRCA2 and RAD51. Interestingly, MRG15-deficient cells, similarly to cells deficient in PALB2 or BRCA2, showed reduced efficiency for homology-directed DNA repair and hypersensitivity to DNA interstrand crosslinking agents. Additionally, knockdown of MRG15 diminished the recruitment of PALB2, BRCA2 and RAD51 to sites of DNA damage and reduced chromatin loading of PALB2 and BRCA2. These results suggest that MRG15 mediates DNA-damage-response functions of the BRCA complex in chromatin.
引用
收藏
页码:1124 / 1130
页数:7
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