title: Condensin dysfunction in human cells induces nonrandom chromosomal breaks in anaphase, with distinct patterns for both unique and repeated genomic regions.
abstract: Condensin complexes are essential for chromosome condensation and segregation in mitosis, while condensin dysfunction, among other pathways leading to chromosomal bridging in mitosis, may play a role in tumor genomic instability, including recently discovered chromotripsis. To characterize potential double-strand breaks specifically occurring in late anaphase, human chromosomes depleted of condensin were analyzed by γ-H2AX ChIP followed by high-throughput sequencing (ChIP-seq). In condensin-depleted cells, the nonrepeated parts of the genome were shown to contain distinct γ-H2AX enrichment zones 75% of which overlapped with known hemizygous deletions in cancers. Furthermore, some tandemly repeated DNA sequences, analyzed separately from the rest of the genome, showed significant γ-H2AX enrichment in condensin-depleted anaphases. The most commonly occurring targets of such enrichment included simple repeats, centromeric satellites, and rDNA. The two latter categories indicate that acrocentric human chromosomes are especially susceptible to breaks upon condensin deficiency. The genomic regions that are specifically destabilized upon condensin dysfunction may constitute a condensin-specific chromosome destabilization pattern.
authors.affiliation: NIH NCI, Genome Structure and Function Section, Bethesda, MD 20892, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Samoshkin
authors.forename: Stanimir
authors.initials: S
authors.lastname: Dulev
authors.forename: Dmitry
authors.initials: D
authors.lastname: Loukinov
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Rosenfeld
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Strunnikov
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000705:Anaphase / Q000502:physiology*; D052160:Benzothiazoles; D047369:Chromatin Immunoprecipitation; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003959:Diamines; D019084:Fluorescent Antibody Technique, Indirect; D015894:Genome, Human / Q000235:genetics*; D006367:HeLa Cells; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D009930:Organic Chemicals; D011804:Quinolines; D034622:RNA Interference; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: D052160:Benzothiazoles; D004268:DNA-Binding Proteins; D003959:Diamines; C468783:H2AX protein, human; D006657:Histones; D046912:Multiprotein Complexes; D009930:Organic Chemicals; D011804:Quinolines; C108312:condensin complexes; C098022:SYBR Green I; D000251:Adenosine Triphosphatases