Breakpoint clusters: reason or consequence?
Chromosomal rearrangements are common causes of cancer. In the majority of cases, the malignancy is induced via an altered transcription factor. The breakpoints of such translocations are often mysteriously tightly clustered in the genome. Even more surprisingly, such breakpoint clusters often contain specific genomic elements, such as topoisomerase II consensus sites, nuclear matrix attachment regions, etc. In this review, we discuss the common idea of breakpoints being induced by chromatin structure. We also touch on the question of whether the structure of corresponding proteins is related to the positions of breakpoints. Finally, we refer to recent works on chromosome territories and their distribution in the interphase nucleus.
Bystritskiy
Andrey A
AA
Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology of the Russian Academy of Sciences, Vavilov Str. 34/5, 119334 Moscow, Russia. abystitskiy@mail.ru
Razin
Sergey V
SV
D001665:Binding Sites; D019457:Chromosome Breakage; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D051788:Myeloid-Lymphoid Leukemia Protein; D009369:Neoplasms / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D015513:Oncogene Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D004250:DNA Topoisomerases, Type II