Retrotransposon reverse-transcriptase-mediated repair of chromosomal breaks

Teng, Shu-Chun; Kim, Bohye; Gabriel, Abram

doi:10.1038/383641a0

Cited by 236 publications

(175 citation statements)

References 22 publications

Supporting

Mentioning

165

Contrasting

Unclassified

Order By: Relevance

“…Retrotransposons can inactivate genes, activate or alter the regulation of adjacent genes, patch together broken chromosome ends (32)(33)(34), and provide dispersed regions of homology that facilitate chromosomal rearrangements (35,36). Although the mutations that they cause are often neutral or deleterious, retrotransposons impart evolutionary plasticity to the genome, thereby contributing to the ability of cells to adapt to new environments (37).…”

Section: Discussionmentioning

confidence: 99%

Activation of a LTR-retrotransposon by telomere erosion

Scholes

Kenny

Gamache

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Retrotransposons can facilitate repair of broken chromosomes, and therefore an important question is whether the host can activate retrotransposons in response to chromosomal lesions. Here we show that Ty1 elements, which are LTR-retrotransposons in Saccharomyces cerevisiae, are mobilized when DNA lesions are created by the loss of telomere function. Inactivation of telomerase in yeast results in progressive shortening of telomeric DNA, eventually triggering a DNA-damage checkpoint that arrests cells in G 2͞M. A fraction of cells, termed survivors, recover from arrest by forming alternative telomere structures. When telomerase is inactivated, Ty1 retrotransposition increases substantially in parallel with telomere erosion and then partially declines when survivors emerge. Retrotransposition is stimulated at the level of Ty1 cDNA synthesis, causing cDNA levels to increase 20-fold or more before survivors form. This response is elicited through a signaling pathway that includes Rad24, Rad17, and Rad9, three components of the DNAdamage checkpoint. Our findings indicate that Ty1 retrotransposons are activated as part of the cellular response to telomere dysfunction.

show abstract

Section: Discussionmentioning

confidence: 99%

Activation of a LTR-retrotransposon by telomere erosion

Scholes

Kenny

Gamache

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…This event appears to be a more complex version of a When both RAD52 and YKU80 were deleted, the overall survival frequency was not significantly lower than phenomenon that we and others previously characterized after a single HO cut, i.e., insertion of segments of that of the yku80 strain by itself. The frequency of FOA resistance among survivors, however, was only 0.26% vs. Ty1 cDNA at a DSB site (Moore and Haber 1996;Teng et al 1996;Yu and Gabriel 1999). the ‫%05ف‬ when RAD52 was present in the cells.…”

Section: Analysis Of Survival After Two Cutsmentioning

confidence: 99%

Reciprocal Translocations inSaccharomyces cerevisiaeFormed by Nonhomologous End Joining

Gabriel

2004

Genetics

Self Cite

View full text Add to dashboard Cite

Reciprocal translocations are common in cancer cells, but their creation is poorly understood. We have developed an assay system in Saccharomyces cerevisiae to study reciprocal translocation formation in the absence of homology. We induce two specific double-strand breaks (DSBs) simultaneously on separate chromosomes with HO endonuclease and analyze the subsequent chromosomal rearrangements among surviving cells. Under these conditions, reciprocal translocations via nonhomologous end joining (NHEJ) occur at frequencies of ‫2ف‬Ϫ7 ϫ 10 Ϫ5 /cell exposed to the DSBs. Yku80p is a component of the cell's NHEJ machinery. In its absence, reciprocal translocations still occur, but the junctions are associated with deletions and extended overlapping sequences. After induction of a single DSB, translocations and inversions are recovered in wild-type and rad52 strains. In these rearrangements, a nonrandom assortment of sites have fused to the DSB, and their junctions show typical signs of NHEJ. The sites tend to be between open reading frames or within Ty1 LTRs. In some cases the translocation partner is formed by a break at a cryptic HO recognition site. Our results demonstrate that NHEJ-mediated reciprocal translocations can form in S. cerevisiae as a consequence of DSB repair.

show abstract

“…On the other hand, it should not be excluded that the presence of the 3Ј-repair activities associated with NL1Tc could be indicative of a possible repair role of the L1Tc element. In fact, repair of double-stranded DNA breaks because of the insertion of the Ty1 element from Saccharomyces cerevisiae in the presence of functional reverse transcriptase (from human L1, yeast Ty1, or Crithidia CRE1) (20,21) has recently been described.…”

Section: Discussionmentioning

confidence: 99%

The L1Tc, Long Interspersed Nucleotide Element from Trypanosoma cruzi, Encodes a Protein with 3′-Phosphatase and 3′-Phosphodiesterase Enzymatic Activities

Olivares

Thomas

Alonso

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

The presence of a long interspersed nucleotide element, named L1Tc, which is actively transcribed in the parasite Trypanosoma cruzi, has been recently described. The open reading frame 1 of this element encodes the NL1Tc protein, which has apurinic/apyrimidinic endonuclease activity and is probably implicated in the first stage of the transposition of the element. In the present paper we show that NL1Tc effectively removes 3 -blocking groups (3 -phosphate and 3 -phosphoglycolate) from damaged DNA substrates. Thus, both 3 -phosphatase and 3 -phosphodiesterase activities are present in NL1Tc. We propose that these enzymatic activities would allow the 3 -blocking ends to function as targets for the insertion of L1Tc element, in addition to the apurinic/apyrimidinic sites previously described. The potential biological function of the NL1Tc protein has also been evidenced by its ability to repair the DNA damage induced by the methyl methanesulfonate alkylating or oxidative agents such as hydrogen peroxide and t-butyl hydroperoxide in Escherichia coli (xth and xth, nfo) mutants.

show abstract

Retrotransposon reverse-transcriptase-mediated repair of chromosomal breaks

Cited by 236 publications

References 22 publications

Activation of a LTR-retrotransposon by telomere erosion

Activation of a LTR-retrotransposon by telomere erosion

Reciprocal Translocations inSaccharomyces cerevisiaeFormed by Nonhomologous End Joining

The L1Tc, Long Interspersed Nucleotide Element from Trypanosoma cruzi, Encodes a Protein with 3′-Phosphatase and 3′-Phosphodiesterase Enzymatic Activities

Contact Info

Product

Resources

About