Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility

被引:102
作者
Voineagu, Irina [1 ,2 ]
Surka, Christine F. [1 ]
Shishkin, Alexander A. [1 ]
Krasilnikova, Maria M. [3 ]
Mirkin, Sergei M. [1 ]
机构
[1] Tufts Univ, Dept Biol, Medford, MA 02155 USA
[2] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA
[3] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA
基金
美国国家卫生研究院;
关键词
SYNTHESIS IN-VITRO; DNA-REPLICATION; TRINUCLEOTIDE REPEATS; X-SYNDROME; S-PHASE; HUMAN-DISEASE; MRC1; FORM; INSTABILITY; TOF1;
D O I
10.1038/nsmb.1527
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
Expanded CGG repeats cause chromosomal fragility and hereditary neurological disorders in humans. Replication forks stall at CGG repeats in a length-dependent manner in primate cells and in yeast. Saccharomyces cerevisiae proteins Tof1 and Mrc1 facilitate replication fork progression through CGG repeats. Remarkably, the fork-stabilizing role of Mrc1 does not involve its checkpoint function. Thus, chromosomal fragility might occur when forks stalled at expanded CGG repeats escape the S-phase checkpoint.
引用
收藏
页码:226 / 228
页数:3
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