Chromosomal Miss-Segregation and DNA damage Consolato Sergi, M.D., Ph.D. University of Alberta...

Chromosomal Miss-Segregation and DNA damage

Consolato Sergi, M.D., Ph.D.University of Alberta Hospital

Chromosomal Miss-segregation and DNA Damage


The ScientistSeptember 29, 2011


Tumor formation may require fewer steps to get

started than previously thought!!! There was a missing link between chromosome

instability (CIN) and DNA damage, which has been

RECENTLY found! Two tumorigenesis triggers typically considered

independent phenomena—can arise from a single

defect in how chromosomes segregate during cell

division.

Chromosomal Miss-Segregation and DNA Damage

• It is important to remind that to divide normally,

cells must ensure that their chromosomes

(# and structure) properly segregate, with each

daughter cell receiving a copy of the duplicated

chromosomes (mitosis). • In the paper the authors noticed that most tumor

cells exhibited both aneuploidy and

structural DNA damage.


• Aneuploidy: Chromosomal abnormality constituted by an abnormal number of chromosomes

• Aneuploidy occurring in products of conception may cause genetic disorders (birth defects)

• Aneuploidy occurring in somatic cells can give rise to cancer.


• In aneuploidy there is the possibility that in the missing

chromosome contains a gene encoding a protein

important for DNA repair.

• Thus, it may lead indirectly to DNA damage!!!


The authors noticed that DNA damage sometimes occurred within a single division following chromosome miss-segregation, before the daughter cells would need to start synthesizing new DNA repair proteins.

Thus, this leads to hypothesize that miss-segregation is directly correlated to damaged DNA.


Janssen et al. Science 2011


1. To cause aneuploidy in dividing human epithelial cells the authors treated them with a chemical that causes spindle fibers to connect a single centromere to both poles of the cell, so that the fibers would not properly split the paired chromosomes.

2. Within hours after division occurred, real-time videos tracking fluorescent staining for DNA damage showed a miss-segregation event correlated with higher levels of DNA damage.

Take Home MessageTake Home Message

1. Two tumorigenesis triggers typically considered independent phenomena—can arise from a singledefect in how chromosomes segregate during celldivision.

2. In aneuploidy there is the possibility of a missing chromosome containing a gene encoding a protein important for DNA repair that may lead indirectly to DNA damage!!!

3. In the future we could develop anti-cancer therapeutics that target chromosome miss-segregation as a central event in the development of both abnormal chromosome number and structural DNA damage.

Chromosomal Miss-Segregation and DNA damage Consolato Sergi, M.D., Ph.D. University of Alberta...

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