2000
DOI: 10.1038/35006670
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DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation

Abstract: Cancer susceptibility genes have been classified into two groups: gatekeepers and caretakers. Gatekeepers are genes that control cell proliferation and death, whereas caretakers are DNA repair genes whose inactivation leads to genetic instability. Abrogation of both caretaker and gatekeeper function markedly increases cancer susceptibility. Although the importance of Ku80 in DNA double-strand break repair is well established, neither Ku80 nor other components of the non-homologous end-joining pathway are known… Show more

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Cited by 508 publications
(422 citation statements)
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“…Notably, tumor #160 contained three non-germline sized fragments where the signal intensity of one was greater than the other two (Figure 1c), analogous to Igh rearrangements in pro-B lymphomas of NHEJ/Tp53-deficient and H2AX/Tp53-deficient mice. These tumors harbor a t(12;15) translocation with 3 0 J H sequences and a t(15;12) translocation with amplified 3 0 J H sequences, which arise following replication of a chromosome 12 harboring un-repaired Igh DSBs, as well as a normal chromosome 12 with 3 0 J H sequences (Difilippantonio et al, 2000;Gao et al, 2000;Bassing et al, 2003;Celeste et al, 2003b). Germline Jk segments reside on an 8.9-kb BamHI fragment (Figure 1d) that changes size upon Vkto-Jk rearrangements or is deleted upon Vk rearrangements to the 3 0 Igk deleting element, each of which occurs in pre-B cells.…”
Section: Resultsmentioning
confidence: 99%
“…Notably, tumor #160 contained three non-germline sized fragments where the signal intensity of one was greater than the other two (Figure 1c), analogous to Igh rearrangements in pro-B lymphomas of NHEJ/Tp53-deficient and H2AX/Tp53-deficient mice. These tumors harbor a t(12;15) translocation with 3 0 J H sequences and a t(15;12) translocation with amplified 3 0 J H sequences, which arise following replication of a chromosome 12 harboring un-repaired Igh DSBs, as well as a normal chromosome 12 with 3 0 J H sequences (Difilippantonio et al, 2000;Gao et al, 2000;Bassing et al, 2003;Celeste et al, 2003b). Germline Jk segments reside on an 8.9-kb BamHI fragment (Figure 1d) that changes size upon Vkto-Jk rearrangements or is deleted upon Vk rearrangements to the 3 0 Igk deleting element, each of which occurs in pre-B cells.…”
Section: Resultsmentioning
confidence: 99%
“…However, a limitation is that mouse studies do not allow a precise dissection and separation of distinct endpoints such as chromosomal instability and survival. The majority of multiple pathway analysis using mice has focused on genetic crosses involving p53 (see for example [30][31][32][33][34]). Since p53 has critical roles in apoptosis and cell cycle checkpoint arrest, the interplay between defined pathways cannot be established.…”
Section: Other Studies Examining the Interplay Between Damage Responsmentioning
confidence: 99%
“…The second and alternative strategy is non-homologous end joining (NHEJ), which ligates the DNA ends without requiring sequence homologies between the two interacting molecules. Defects in HR or in NHEJ can lead to genome instability and tumorigenesis (Liu et al, 1998;Sonoda et al, 1998;Difilippantonio et al, 2000;Ferguson et al, 2000a;Bertrand et al, 2003). However, both functional HR and NHEJ can be responsible for genome rearrangements: (i) functional HR between repeated sequences dispersed through the genome can also lead to genome rearrangements (Purandare and Patel, 1997;Richardson and Jasin, 2000b;Bertrand et al, 2004), and (ii) functional Ku autoantigen protein (KU)-dependent as well as KU-independent NHEJ can generate genetic rearrangements (Guirouilh-Barbat et al, 2004).…”
Section: Introductionmentioning
confidence: 99%