Accession Number : ADA598784


Title :   Function of ZFAND3 in the DNA Damage Response


Descriptive Note : Annual summary rept. 1 Jun 2010-31 May 2013


Corporate Author : VANDERBILT UNIV NASHVILLE TN


Personal Author(s) : Sirbu, Bianca M


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a598784.pdf


Report Date : Jun 2013


Pagination or Media Count : 108


Abstract : Tumors exhibit genomic instability that arises from environmental and endogenous sources of DNA damage. To prevent the propagation of unstable genomes, the DNA damage response (DDR) pathway is activated during each cell cycle to ensure accurate DNA replication, repair of damaged DNA and apoptosis of heavily damaged cells. Thus, the DDR pathway functions as a barrier to cancer. DDR activation has been observed in precancerous lesions and has led to the idea that unresolved problems accumulated during DNA replication promote tumorigenesis. Such damaged sites halt the progression of DNA polymerases and cause replication stress that activates the DDR. Repair and restart of damaged replication forks requires the concerted effort of several DNA repair proteins, including the tumor suppressor BRCA1 (breast cancer 1) and other DDR proteins that have yet to be characterized. I hypothesized that multiple DDR pathways prevent the accumulation of replication stress observed in precancerous and cancerous lesions of the breast. I identified one putative novel replication stress response protein (Zfand3) and characterized its regulation and function during the DDR. I also developed a new biochemical purification method termed iPOND (isolation of proteins on nascent DNA) to examine Zfand3 and other replication stress proteins that function at moving and stalled replication forks in human cells. These findings suggest that multiple DDR pathways coordinated at replication forks prevent genome instability and have implications for understanding breast cancer etiology.


Descriptors :   *BREAST CANCER , *DEOXYRIBONUCLEIC ACIDS , *NEOPLASMS , APOPTOSIS , BIOCHEMISTRY , CELLS(BIOLOGY) , DAMAGE , ETIOLOGY , GENOME , HUMANS , LESIONS , MAMMARY GLANDS , MEDICAL RESEARCH , MOTION , PROPAGATION , PROTEINS , PURIFICATION , RESPONSE


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE