End joining at Caenorhabditis elegans telomeres.
Critically shortened telomeres can be subjected to DNA repair events that generate end-to-end chromosome fusions. The resulting dicentric chromosomes can enter breakage-fusion-bridge cycles, thereby impeding elucidation of the structures of the initial fusion events and a mechanistic understanding of their genesis. Current models for the molecular basis of fusion of critically shortened, uncapped telomeres rely on PCR assays that typically capture fusion breakpoints created by direct ligation of chromosome ends. Here we use independent approaches that rely on distinctive features of Caenorhabditis elegans to study the frequency of direct end-to-end chromosome fusion in telomerase mutants: (1) holocentric chromosomes that allow for genetic isolation of stable end-to-end fusions and (2) unique subtelomeric sequences that allow for thorough PCR analysis of samples of genomic DNA harboring multiple end-to-end fusions. Surprisingly, only a minority of end-to-end fusion events resulted from direct end joining with no additional genome rearrangements. We also demonstrate that deficiency for the C. elegans Ku DNA repair heterodimer does not affect telomere length or cause synthetic effects in the absence of telomerase.
Lowden
Mia Rochelle
MR
Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599.
Meier
Bettina
B
Lee
Teresa Wei-Sy
TW
Hall
Julie
J
Ahmed
Shawn
S
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism; D011088:DNA Ligases / Q000378:metabolism; D004260:DNA Repair; D008957:Models, Genetic; D009154:Mutation; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
D019098:Telomerase; D011088:DNA Ligases
Bioessays. 2004 Nov;26(11):1164-74
15499579
Curr Biol. 2001 Aug 7;11(15):1192-6
11516951
Nucleic Acids Res. 2000 Jul 1;28(13):2585-96
10871410
Nature. 2000 Mar 30;404(6777):510-4
10761921
Mol Cell. 2001 Jan;7(1):55-63
11172711
Genetics. 1998 Apr;148(4):1507-24
9560370
Nucleic Acids Res. 1996 Dec 1;24(23):4639-48
8972848
Cell. 1998 Feb 6;92(3):401-13
9476899
DNA Repair (Amst). 2005 Nov 21;4(11):1215-26
15979949
Nucleic Acids Res. 2006 Jan 10;34(1):96-103
16407328
Nature. 1990 May 31;345(6274):458-60
2342578
EMBO J. 2005 Sep 7;24(17):3128-35
16096639
Genes Dev. 1997 Feb 15;11(4):528-40
9042865
Nucleic Acids Res. 2006 May 08;34(8):2408-17
16682448
Annu Rev Genet. 2006;40:237-77
16822175
Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10770-5
10485901
EMBO J. 2007 Jan 10;26(1):170-83
17159906
EMBO J. 1996 Sep 16;15(18):5093-103
8890183
Mol Cell Biol. 1996 May;16(5):2164-73
8628283
Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8983-8
8799140
DNA Repair (Amst). 2006 Nov 8;5(11):1299-306
16798109
Genetics. 2007 Mar;175(3):1035-45
17237517
EMBO J. 2005 Sep 7;24(17):3117-27
16096640
Genetics. 1999 Dec;153(4):1873-83
10581292
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15084-8
11742099
Mol Cell Biol. 2003 Dec;23(23):8820-8
14612421
Curr Biol. 1998 Dec 17-31;8(25):1395-8
9889105
Cell. 1985 Dec;43(2 Pt 1):405-13
3907856
Eukaryot Cell. 2004 Apr;3(2):369-84
15075267
Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16370-5
17060623
Curr Biol. 2001 Dec 11;11(24):1934-44
11747819
Mol Cell. 2007 May 11;26(3):323-34
17499040
Curr Biol. 1998 May 21;8(11):657-60
9635193
J Theor Biol. 1973 Sep 14;41(1):181-90
4754905
Nature. 1995 Aug 3;376(6539):403-9
7630414
Genes Dev. 2005 Sep 15;19(18):2100-10
16166375
Genes Cells. 1999 Feb;4(2):77-85
10320474
Science. 1997 Mar 7;275(5305):1478-81
9045613
Nature. 1990 Aug 30;346(6287):866-8
2392154
Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10854-9
12963812
Genetics. 2003 Mar;163(3):843-56
12663527
Trends Genet. 1999 Feb;15(2):51-8
10098407
EMBO J. 2000 Jul 17;19(14):3822-30
10899135
Genetics. 2006 Jul;173(3):1301-17
16702421
Genetics. 1982 Nov;102(3):379-400
6890921
EMBO J. 2004 Jun 2;23(11):2304-13
15141167
Curr Biol. 2002 Oct 1;12(19):1635-44
12361565
Cell. 2001 Oct 5;107(1):67-77
11595186
Mol Cell Biol. 2007 Mar;27(6):2253-65
17145779
Nat New Biol. 1972 Oct 18;239(94):197-201
4507727
Cell. 1987 Dec 24;51(6):887-98
3319189
Chromosoma. 2003 Oct;112(3):116-23
14579127
EMBO J. 2002 Jun 3;21(11):2819-26
12032094
Trends Biochem Sci. 2005 Jul;30(7):388-95
15936947
PLoS Genet. 2006 Feb;2(2):e18
16477310
Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):611-5
12511598
Mol Cell Biol. 2001 Jun;21(11):3642-51
11340158
Genetics. 1941 Mar;26(2):234-82
17247004
Cell. 2001 Aug 10;106(3):275-86
11509177
Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14899-904
10611310
Genes Dev. 2007 Oct 1;21(19):2495-508
17908935
EMBO Rep. 2000 Sep;1(3):244-52
11256607
EMBO J. 2002 May 1;21(9):2207-19
11980718
Nature. 2000 Jan 13;403(6766):159-64
10646593
Mol Biol Cell. 2000 Oct;11(10):3265-75
11029034
Genetics. 1986 Jul;113(3):621-39
3732788