Department of Cell Biology

Carl Schildkraut, PhD


Professor, Department of Cell Biology
Chanin Bldg., Room 416

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The Centromere and alpha satellite DNA and the tau protein
Genomic Instability
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Our laboratory is a part of the Institute for Aging Research, the Einstein Stem Cell Institute Center and the Cancer Center.

A major interest of our lab is the organization and regulation of the DNA replication program in mammalian cells and its effect on gene expression. One area we have been concentrating on the role of DNA replication in neuronal diseases such as Alzheimer's. Alzheimer’s disease (AD) is a neuro-degenerative disease that has been studied for more than three decades. Surprisingly after all this effort, there is still no unequivocal treatment and the cause is not known.

We are also focused on understanding the role of genomic instability at human chromosomal fragile sites in cancer and aging.

Genomic Instability can result in cancer and neurological disease. Regions that we study in our lab include alpha satellite DNA (located at centromeres), rDNA genes, telomeres and common fragile sites (CFS). Aberrant replication these fragile regions can result in chromosomal rearrangements that have pathological consequences. One of our overall goals is to elucidate how these distinct classes of biologically important chromosomal fragile sites, are accurately replicated. The knowledge obtained from our studies will provide an essential understanding of how fragile sites are repaired and replicated after DNA damage to prevent genetic dysfunction.

Long-term interests:

  • Difficult to replicate regions accumulate secondary structures which, if not properly resolved, may block DNA replication fork movement and lead to genome instability. We are studying mechanisms to resolve these barriers for efficient and faithful DNA replication.
  • The role of DNA replication of genes involved in neurological diseases such as Alzheimer's. We will examine critical genes in the brain that undergo mutations with aging.
  • Genome protection by telomeres.
  • Regulation and reprogramming of DNA replication of human embryonic stem (ES) cells and induced pluripotent stem cells (iPS).
  • Mechanisms leading to breaks at sites that result in chromosomal rearrangements frequently detected in cancer cells.

Current projects include a wide range of interests:

  • The replication of two repeated sequence DNAs that are involved in Alzheimer's disease: alpha satellite DNA and the ribosomal DNA genes .
  • The DNA2 nuclease/helicase can cleave G-quadruplex structures which are one of the most common non-B structures present in DNA. We study the effect on the deletion of DNA2 on DNA replication.
  • Replication of the alpha satellite DNA at centromeres of specific human chromosomes. These include chromosome 21 and the Y chromosome. The Y chromosome is lost with aging and we are studying the replication of this chromosome to understand more about this loss. Chr 21 undergoes trisomy in Down syndrome and people with Down syndrome have a higher risk of getting Alzheimer's symptoms.

The centromere is a critical element of all mammalian chromosomes. It regulates chromosome segregation and damage to the centromere can result in aneuploidy which results in 25% of all types of miscarriages.

Alpha satellite DNA sequences are located at all centromeres and play an important role in the organization of the centromere. These are repeated sequences which have been difficult to study until recently. We are able to use the single molecule approach we have developed to study the replication of this satellite DNA in individual human chromosomes. It has been shown that the tau protein which plays a major role in Alzheimer's disease interacts with alpha satellite DNA and we are carrying out studies to understand the importance of this interaction.