#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Competitive Repair by Naturally Dispersed Repetitive DNA during Non-Allelic Homologous Recombination


Genome rearrangements often result from non-allelic homologous recombination (NAHR) between repetitive DNA elements dispersed throughout the genome. Here we systematically analyze NAHR between Ty retrotransposons using a genome-wide approach that exploits unique features of Saccharomyces cerevisiae purebred and Saccharomyces cerevisiae/Saccharomyces bayanus hybrid diploids. We find that DNA double-strand breaks (DSBs) induce NAHR–dependent rearrangements using Ty elements located 12 to 48 kilobases distal to the break site. This break-distal recombination (BDR) occurs frequently, even when allelic recombination can repair the break using the homolog. Robust BDR–dependent NAHR demonstrates that sequences very distal to DSBs can effectively compete with proximal sequences for repair of the break. In addition, our analysis of NAHR partner choice between Ty repeats shows that intrachromosomal Ty partners are preferred despite the abundance of potential interchromosomal Ty partners that share higher sequence identity. This competitive advantage of intrachromosomal Tys results from the relative efficiencies of different NAHR repair pathways. Finally, NAHR generates deleterious rearrangements more frequently when DSBs occur outside rather than within a Ty repeat. These findings yield insights into mechanisms of repeat-mediated genome rearrangements associated with evolution and cancer.


Vyšlo v časopise: Competitive Repair by Naturally Dispersed Repetitive DNA during Non-Allelic Homologous Recombination. PLoS Genet 6(12): e32767. doi:10.1371/journal.pgen.1001228
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001228

Souhrn

Genome rearrangements often result from non-allelic homologous recombination (NAHR) between repetitive DNA elements dispersed throughout the genome. Here we systematically analyze NAHR between Ty retrotransposons using a genome-wide approach that exploits unique features of Saccharomyces cerevisiae purebred and Saccharomyces cerevisiae/Saccharomyces bayanus hybrid diploids. We find that DNA double-strand breaks (DSBs) induce NAHR–dependent rearrangements using Ty elements located 12 to 48 kilobases distal to the break site. This break-distal recombination (BDR) occurs frequently, even when allelic recombination can repair the break using the homolog. Robust BDR–dependent NAHR demonstrates that sequences very distal to DSBs can effectively compete with proximal sequences for repair of the break. In addition, our analysis of NAHR partner choice between Ty repeats shows that intrachromosomal Ty partners are preferred despite the abundance of potential interchromosomal Ty partners that share higher sequence identity. This competitive advantage of intrachromosomal Tys results from the relative efficiencies of different NAHR repair pathways. Finally, NAHR generates deleterious rearrangements more frequently when DSBs occur outside rather than within a Ty repeat. These findings yield insights into mechanisms of repeat-mediated genome rearrangements associated with evolution and cancer.


Zdroje

1. StankiewiczP

LupskiJR

2010 Structural variation in the human genome and its role in disease. Annu Rev Med 61 437 455

2. KorbelJO

UrbanAE

AffourtitJP

GodwinB

GrubertF

2007 Paired-end mapping reveals extensive structural variation in the human genome. Science 318 420 426

3. KiddJM

CooperGM

DonahueWF

HaydenHS

SampasN

2008 Mapping and sequencing of structural variation from eight human genomes. Nature 453 56 64

4. HanK

LeeJ

MeyerTJ

RemediosP

GoodwinL

2008 L1 recombination-associated deletions generate human genomic variation. Proc Natl Acad Sci U S A 105 19366 19371

5. XingJ

ZhangY

HanK

SalemAH

SenSK

2009 Mobile elements create structural variation: analysis of a complete human genome. Genome Res 19 1516 1526

6. PaquesF

HaberJE

1999 Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 63 349 404

7. SugawaraN

HaberJE

1992 Characterization of double-strand break-induced recombination: homology requirements and single-stranded DNA formation. Mol Cell Biol 12 563 575

8. RudinN

HaberJE

1988 Efficient repair of HO-induced chromosomal breaks in Saccharomyces cerevisiae by recombination between flanking homologous sequences. Mol Cell Biol 8 3918 3928

9. RayA

MachinN

StahlFW

1989 A DNA double chain break stimulates triparental recombination in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 86 6225 6229

10. InbarO

KupiecM

1999 Homology search and choice of homologous partner during mitotic recombination. Mol Cell Biol 19 4134 4142

11. DattaA

HendrixM

LipsitchM

Jinks-RobertsonS

1997 Dual roles for DNA sequence identity and the mismatch repair system in the regulation of mitotic crossing-over in yeast. Proc Natl Acad Sci U S A 94 9757 9762

12. LarocqueJR

JasinM

2010 Mechanisms of recombination between diverged sequences in wild-type and BLM-deficient mouse and human cells. Mol Cell Biol

13. ShenP

HuangHV

1986 Homologous recombination in Escherichia coli: dependence on substrate length and homology. Genetics 112 441 457

14. WaldmanAS

LiskayRM

1988 Dependence of intrachromosomal recombination in mammalian cells on uninterrupted homology. Mol Cell Biol 8 5350 5357

15. Jinks-RobertsonS

MichelitchM

RamcharanS

1993 Substrate length requirements for efficient mitotic recombination in Saccharomyces cerevisiae. Mol Cell Biol 13 3937 3950

16. RoederGS

SmithM

LambieEJ

1984 Intrachromosomal movement of genetically marked Saccharomyces cerevisiae transposons by gene conversion. Mol Cell Biol 4 703 711

17. LichtenM

HaberJE

1989 Position effects in ectopic and allelic mitotic recombination in Saccharomyces cerevisiae. Genetics 123 261 268

18. AgmonN

PurS

LiefshitzB

KupiecM

2009 Analysis of repair mechanism choice during homologous recombination. Nucleic Acids Res 37 5081 5092

19. BurgessSM

KlecknerN

1999 Collisions between yeast chromosomal loci in vivo are governed by three layers of organization. Genes Dev 13 1871 1883

20. SchlechtHB

LichtenM

GoldmanAS

2004 Compartmentalization of the yeast meiotic nucleus revealed by analysis of ectopic recombination. Genetics 168 1189 1203

21. MalkovaA

NaylorML

YamaguchiM

IraG

HaberJE

2005 RAD51-dependent break-induced replication differs in kinetics and checkpoint responses from RAD51-mediated gene conversion. Mol Cell Biol 25 933 944

22. WuX

WuC

HaberJE

1997 Rules of donor preference in saccharomyces mating-type gene switching revealed by a competition assay involving two types of recombination. Genetics 147 399 407

23. LiangF

HanM

RomanienkoPJ

JasinM

1998 Homology-directed repair is a major double-strand break repair pathway in mammalian cells. Proc Natl Acad Sci U S A 95 5172 5177

24. NeuvegliseC

FeldmannH

BonE

GaillardinC

CasaregolaS

2002 Genomic evolution of the long terminal repeat retrotransposons in hemiascomycetous yeasts. Genome Res 12 930 943

25. LitiG

PeruffoA

JamesSA

RobertsIN

LouisEJ

2005 Inferences of evolutionary relationships from a population survey of LTR-retrotransposons and telomeric-associated sequences in the Saccharomyces sensu stricto complex. Yeast 22 177 192

26. LeeHY

ChouJY

CheongL

ChangNH

YangSY

2008 Incompatibility of nuclear and mitochondrial genomes causes hybrid sterility between two yeast species. Cell 135 1065 1073

27. KellisM

PattersonN

EndrizziM

BirrenB

LanderES

2003 Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 423 241 254

28. JainS

SugawaraN

LydeardJ

VazeM

Tanguy Le GacN

2009 A recombination execution checkpoint regulates the choice of homologous recombination pathway during DNA double-strand break repair. Genes Dev 23 291 303

29. SpellRM

Jinks-RobertsonS

2004 Examination of the roles of Sgs1 and Srs2 helicases in the enforcement of recombination fidelity in Saccharomyces cerevisiae. Genetics 168 1855 1865

30. Fishman-LobellJ

RudinN

HaberJE

1992 Two alternative pathways of double-strand break repair that are kinetically separable and independently modulated. Mol Cell Biol 12 1292 1303

31. SugawaraN

WangX

HaberJE

2003 In vivo roles of Rad52, Rad54, and Rad55 proteins in Rad51-mediated recombination. Mol Cell 12 209 219

32. ArguesoJL

WestmorelandJ

MieczkowskiPA

GawelM

PetesTD

2008 Double-strand breaks associated with repetitive DNA can reshape the genome. Proc Natl Acad Sci U S A 105 11845 11850

33. ParketA

InbarO

KupiecM

1995 Recombination of Ty elements in yeast can be induced by a double-strand break. Genetics 140 67 77

34. VanHulleK

LemoineFJ

NarayananV

DowningB

HullK

2007 Inverted DNA repeats channel repair of distant double-strand breaks into chromatid fusions and chromosomal rearrangements. Mol Cell Biol 27 2601 2614

35. LeePS

PetesTD

2010 From the Cover: mitotic gene conversion events induced in G1-synchronized yeast cells by gamma rays are similar to spontaneous conversion events. Proc Natl Acad Sci U S A 107 7383 7388

36. ChungWH

ZhuZ

PapushaA

MalkovaA

IraG

2010 Defective resection at DNA double-strand breaks leads to de novo telomere formation and enhances gene targeting. PLoS Genet 6 e1000948 doi:10.1371/journal.pgen.1000948

37. MarshallWF

StraightA

MarkoJF

SwedlowJ

DernburgA

1997 Interphase chromosomes undergo constrained diffusional motion in living cells. Curr Biol 7 930 939

38. DuanZ

AndronescuM

SchutzK

McIlwainS

KimYJ

2010 A three-dimensional model of the yeast genome. Nature 465 363 367

39. KimJM

VanguriS

BoekeJD

GabrielA

VoytasDF

1998 Transposable elements and genome organization: a comprehensive survey of retrotransposons revealed by the complete Saccharomyces cerevisiae genome sequence. Genome Res 8 464 478

40. ThompsonM

HaeuslerRA

GoodPD

EngelkeDR

2003 Nucleolar clustering of dispersed tRNA genes. Science 302 1399 1401

41. Johnson-SchlitzDM

FloresC

EngelsWR

2007 Multiple-pathway analysis of double-strand break repair mutations in Drosophila. PLoS Genet 3 e50 doi:10.1371/journal.pgen.0030050

42. ElliottB

RichardsonC

JasinM

2005 Chromosomal translocation mechanisms at intronic alu elements in mammalian cells. Mol Cell 17 885 894

43. TremblayA

JasinM

ChartrandP

2000 A double-strand break in a chromosomal LINE element can be repaired by gene conversion with various endogenous LINE elements in mouse cells. Mol Cell Biol 20 54 60

44. UmezuK

HiraokaM

MoriM

MakiH

2002 Structural analysis of aberrant chromosomes that occur spontaneously in diploid Saccharomyces cerevisiae: retrotransposon Ty1 plays a crucial role in chromosomal rearrangements. Genetics 160 97 110

45. GuthrieC

FinkGR

1991 Guide to Yeast Genetics and Molecular Biology. San Diego, California Academic Press, Inc.

46. BrachmannCB

DaviesA

CostGJ

CaputoE

LiJ

1998 Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications. Yeast 14 115 132

47. MartinOC

DeSevoCG

GuoBZ

KoshlandDE

DunhamMJ

2009 Telomere behavior in a hybrid yeast. Cell Res 19 910 912

48. GietzRD

SchiestlRH

2007 High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method. Nat Protoc 2 31 34

49. LisbyM

MortensenUH

RothsteinR

2003 Colocalization of multiple DNA double-strand breaks at a single Rad52 repair centre. Nat Cell Biol 5 572 577

50. Fishman-LobellJ

HaberJE

1992 Removal of nonhomologous DNA ends in double-strand break recombination: the role of the yeast ultraviolet repair gene RAD1. Science 258 480 484

51. HaberJE

1992 Mating-type gene switching in Saccharomyces cerevisiae. Trends Genet 8 446 452

52. SchwartzDC

CantorCR

1984 Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis. Cell 37 67 75

53. DunhamMJ

BadraneH

FereaT

AdamsJ

BrownPO

2002 Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 99 16144 16149

54. WicksteedBL

CollinsI

DershowitzA

StatevaLI

GreenRP

1994 A physical comparison of chromosome III in six strains of Saccharomyces cerevisiae. Yeast 10 39 57

55. LemoineFJ

DegtyarevaNP

LobachevK

PetesTD

2005 Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites. Cell 120 587 598

56. ShibataY

MalhotraA

BekiranovS

DuttaA

2009 Yeast genome analysis identifies chromosomal translocation, gene conversion events and several sites of Ty element insertion. Nucleic Acids Res 37 6454 6465

57. GordonD

AbajianC

GreenP

1998 Consed: a graphical tool for sequence finishing. Genome Res 8 195 202

58. RiceP

LongdenI

BleasbyA

2000 EMBOSS: the European Molecular Biology Open Software Suite. Trends Genet 16 276 277

59. AltschulSF

GishW

MillerW

MyersEW

LipmanDJ

1990 Basic local alignment search tool. J Mol Biol 215 403 410

60. StajichJE

BlockD

BoulezK

BrennerSE

ChervitzSA

2002 The Bioperl toolkit: Perl modules for the life sciences. Genome Res 12 1611 1618

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2010 Číslo 12
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#