Unknown

Dataset Information

0

C-Myc induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus.


ABSTRACT: In previous work, we showed that telomeres of normal cells are organized within the 3D space of the interphase nucleus in a nonoverlapping and cell cycle-dependent manner. This order is distorted in tumor cell nuclei where telomeres are found in close association forming aggregates of various numbers and sizes. Here we show that c-Myc overexpression induces telomeric aggregations in the interphase nucleus. Directly proportional to the duration of c-Myc deregulation, we observe three or five cycles of telomeric aggregate formation in interphase nuclei. These cycles reflect the onset and propagation of breakage-bridge-fusion cycles that are initiated by end-to-end telomeric fusions of chromosomes. Subsequent to initial chromosomal breakages, new fusions follow and the breakage-bridge-fusion cycles continue. During this time, nonreciprocal translocations are generated. c-Myc-dependent remodeling of the organization of telomeres thus precedes the onset of genomic instability and subsequently leads to chromosomal rearrangements. Our findings reveal that c-Myc possesses the ability to structurally modify chromosomes through telomeric fusions, thereby reorganizing the genetic information.

SUBMITTER: Louis SF 

PROVIDER: S-EPMC1172233 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

c-Myc induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus.

Louis Sherif F SF   Vermolen Bart J BJ   Garini Yuval Y   Young Ian T IT   Guffei Amanda A   Lichtensztejn Zelda Z   Kuttler Fabien F   Chuang Tony C Y TC   Moshir Sharareh S   Mougey Virginie V   Chuang Alice Y C AY   Kerr Paul Donald PD   Fest Thierry T   Boukamp Petra P   Mai Sabine S  

Proceedings of the National Academy of Sciences of the United States of America 20050627 27


In previous work, we showed that telomeres of normal cells are organized within the 3D space of the interphase nucleus in a nonoverlapping and cell cycle-dependent manner. This order is distorted in tumor cell nuclei where telomeres are found in close association forming aggregates of various numbers and sizes. Here we show that c-Myc overexpression induces telomeric aggregations in the interphase nucleus. Directly proportional to the duration of c-Myc deregulation, we observe three or five cycl  ...[more]

Similar Datasets

| S-EPMC9245672 | biostudies-literature
| S-EPMC5371638 | biostudies-literature
| S-EPMC3014980 | biostudies-literature
| S-EPMC3366409 | biostudies-literature
| S-EPMC6358699 | biostudies-literature
| S-EPMC7594495 | biostudies-literature
| S-EPMC6822454 | biostudies-literature
| S-EPMC3471523 | biostudies-literature
| S-EPMC5473940 | biostudies-literature
| S-EPMC6733473 | biostudies-literature