Repeat instability: Mechanisms of dynamic mutations

被引：670

作者：

Pearson, CE

Edamura, KN

Cleary, JD

机构：

[1] Hosp Sick Children, Program Genet & Genom Biol, Toronto, ON M5G 1L7, Canada

[2] Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada

来源：

NATURE REVIEWS GENETICS | 2005年 / 6卷 / 10期

基金：

加拿大健康研究院;

关键词：

D O I：

10.1038/nrg1689

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Disease-causing repeat instability is an important and unique form of mutation that is linked to more than 40 neurological, neurodegenerative and neuromuscular disorders. DNA repeat expansion mutations are dynamic and ongoing within tissues and across generations. The patterns of inherited and tissue-specific instability are determined by both gene-specific cis-elements and trans-acting DNA metabolic proteins. Repeat instability probably involves the formation of unusual DNA structures during DNA replication, repair and recombination. Experimental advances towards explaining the mechanisms of repeat instability have broadened our understanding of this mutational process. They have revealed surprising ways in which metabolic pathways can drive or protect from repeat instability.

引用

收藏

页码：729 / 742

页数：14

相关论文

共 169 条

[1] Transgenic mice with an expanded CAG repeat controlled by the human AR promoter show polyglutamine nuclear inclusions and neuronal dysfunction without neuronal cell death [J].

Adachi, H ;

Kume, A ;

Li, M ;

Nakagomi, Y ;

Niwa, H ;

Do, J ;

Sang, C ;

Kobayashi, Y ;

Doyu, M ;

Sobue, G .

HUMAN MOLECULAR GENETICS, 2001, 10 (10) :1039-1048

[2] GAA repeat instability in Friedreich ataxia YAC transgenic mice [J].

Al-Mahdawi, S ;

Pinto, RM ;

Ruddle, P ;

Carroll, C ;

Webster, Z ;

Pook, M .

GENOMICS, 2004, 84 (02) :301-310

[3] Larger CAG expansions in skeletal muscle compared with lymphocytes in Kennedy disease but not in Huntington disease [J].

Ansved, T ;

Lundin, A ;

Anvret, M .

NEUROLOGY, 1998, 51 (05) :1442-1444

[4] Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines [J].

Beilin, J ;

Ball, EMA ;

Favaloro, JM ;

Zajac, JD .

JOURNAL OF MOLECULAR ENDOCRINOLOGY, 2000, 25 (01) :85-96

[5] SOMATIC STABILITY IN CHORIONIC VILLI SAMPLES AND OTHER HUNTINGTON FETAL TISSUES [J].

BENITEZ, J ;

ROBLEDO, M ;

RAMOS, C ;

AYUSO, C ;

ASTARLOA, R ;

YEBENES, JG ;

BRAMBATI, B .

HUMAN GENETICS, 1995, 96 (02) :229-232

[6] Transcription increases the deletion frequency of long CTG center dot CAG triplet repeats from plasmids in Escherichia coli [J].

Bowater, RP ;

Jaworski, A ;

Larson, JE ;

Parniewski, P ;

Wells, RD .

NUCLEIC ACIDS RESEARCH, 1997, 25 (14) :2861-2868

[7] Cis-acting modifiers of expanded CAG CTG triplet repeat expandability:: associations with flanking GC content and proximity to CpG islands [J].

Brock, GJR ;

Anderson, NH ;

Monckton, DG .

HUMAN MOLECULAR GENETICS, 1999, 8 (06) :1061-1067

[8] Alanine tracts: the expanding story of human illness and trinucleotide repeats [J].

Brown, LY ;

Brown, SA .

TRENDS IN GENETICS, 2004, 20 (01) :51-58

[9] Fully expanded FMR1 CGG repeats exhibit a length- and differentiation-dependent instability in cell hybrids that is independent of DNA methylation [J].

Burman, RW ;

Popovich, BW ;

Jacky, PB ;

Turker, MS .

HUMAN MOLECULAR GENETICS, 1999, 8 (12) :2293-2302

[10] Mutations in yeast replication proteins that increase CAG/CTG expansions also increase repeat fragility [J].

Callahan, JL ;

Andrews, KJ ;

Zakian, VA ;

Freudenreich, CH .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (21) :7849-7860

← 1 2 3 4 5 6 7 8 9 10 →