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Multiple pathways suppress telomere addition to DNA breaks in the Drosophila germline

, : Multiple pathways suppress telomere addition to DNA breaks in the Drosophila germline. Genetics 191(2): 407-417

Telomeres protect chromosome ends from being repaired as double-strand breaks (DSBs). Just as DSB repair is suppressed at telomeres, de novo telomere addition is suppressed at the site of DSBs. To identify factors responsible for this suppression, we developed an assay to monitor de novo telomere formation in Drosophila, an organism in which telomeres can be established on chromosome ends with essentially any sequence. Germline expression of the I-SceI endonuclease resulted in precise telomere formation at its cut site with high efficiency. Using this assay, we quantified the frequency of telomere formation in different genetic backgrounds with known or possible defects in DNA damage repair. We showed that disruption of DSB repair factors (Rad51 or DNA ligase IV) or DSB sensing factors (ATRIP or MDC1) resulted in more efficient telomere formation. Interestingly, partial disruption of factors that normally regulate telomere protection (ATM or NBS) also led to higher frequencies of telomere formation, suggesting that these proteins have opposing roles in telomere maintenance vs. establishment. In the ku70 mutant background, telomere establishment was preceded by excessive degradation of DSB ends, which were stabilized upon telomere formation. Most strikingly, the removal of ATRIP caused a dramatic increase in telomeric retrotransposon attachment to broken ends. Our study identifies several pathways that suppress telomere addition at DSBs, paving the way for future mechanistic studies.


PMID: 22446318

DOI: 10.1534/genetics.112.138818

Other references

Attané, J.P.; Ravelosona, D.; Marty, A.; Samson, Y.; Chappert, C., 2006: Thermally activated depinning of a narrow domain wall from a single defect. We describe the field induced depinning process of a magnetic domain wall (DW) from a single bidimensional nanometric defect. The DW propagates in a wire lithographed on a film with strong perpendicular anisotropy. We observe a statistical distrib...

Kwak, M-Kyoung.; Wakabayashi, N.; Itoh, K.; Motohashi, H.; Yamamoto, M.; Kensler, T.W., 2002: Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival. Enzyme inducers such as 3H-1,2-dithiole-3-thione (D3T) enhance the detoxication of environmental carcinogens and protect against neoplasia. The putative molecular sensor for inducers is Keap1, a sulfhydryl-rich protein that sequesters the transcri...

Mace, D., 2002: AIDS centers of excellence. Tennessee Medicine 95(2): 70-71

Bîscă, N.; Duţu, S.; Jienescu, Z.; Fierbinţeanu, O.; Murgoci, F., 1985: Respiratory function study of the lung in children with chronic respiratory symptoms. I. Bronchial asthma. Revista de Pediatrie, Obstetrica Si Ginecologie. Pediatria 34(3): 261-270

Crandall R.C.; Wagner F.W.Jr, 1981: Partial and total calcanectomy a review of 31 cases over a 10 year period. Partial (20) and 11 total calcanectomies were performed in 29 patients, 18 of whom were diabetics with heel ulcerations. All but 2 had osteomyelitis of the calcaneus. Of the patients, 8 had spine injury. The remaining patients had conditions in wh...

Schulte, D.J., 2004: Mandatory reporting of medical record information after HIPAA. Michigan Medicine 103(2): 6-6

Wong, Y-Guang.; Wang, Y-Xiong.; Liu, X-Qing.; He, J-Lin.; Chen, X-Mei.; Feng, Y-Hong., 2005: Relationship of expression of leukemia inhibitory factor gene with progesterone and estradiol in mouse endometrium. Leukemia inhibitory factor(LIF) is a glycoprotein with multiple activities, it expresses violently in most mice endometrium on 4-5 day of pregnancy,however the mechanism of LIF gene expression was not known completely. LIF gene expression was exam...

Cho, B.K.; Lee, M.; Oh, N.K.; Zin, W.C., 2001: Chain length-dependent three-dimensional organization of molecular rods with flexible coils. Journal of the American Chemical Society 123(39): 9677-9678

Courvoisier Joan M., 1974: Correlation of spores from the Pennsylvanian coal ball fructifications with dispersed spores from Pennsylvanian coal. American Journal of Botany 61(5, Suppl

Hoc, Ps, 1984: The genus Cathormion (Leguminosae, Mimosoideae) in Argentina. Study of the pollen. Darwiniana 5(25): 163-170