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DNA Repair During DNA Replication
Author(s) -
Cortez David
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.500.1
Subject(s) - replisome , biology , dna replication , dna damage , dna re replication , eukaryotic dna replication , genetics , epigenetics , control of chromosome duplication , dna repair , pre replication complex , dna , replication protein a , microbiology and biotechnology , computational biology , dna binding protein , gene , transcription factor
Successful DNA replication is essential to maintain genome integrity and prevent disease. In human cells, over 6 billion base pairs of DNA need to be replicated accurately and packaged into chromatin each cell division cycle. Furthermore, these processes must occur in the context of defects in the DNA template such as DNA damage, which present challenges to both genetic and epigenetic inheritance. The replisome is a highly regulated, dynamic machine that must work with speed and precision to duplicate the chromosomes successfully. Failures during DNA replication cause mutations, epigenetic changes, and other chromosomal aberrations that ultimately cause disease such as cancer. We recently developed a methodology called iPOND to isolate proteins on nascent DNA. Combining iPOND with quantitative mass spectrometry permits a detailed examination of the replisome and DNA damage response machineries. I will present how we have used this method to examine the functions of ATR in maintaining replisome stability and promoting replication fork restart. Also, I will demonstrate how monitoring protein abundance in multiple experimental conditions with iPOND is sufficient to identify protein complexes and new replisome and DNA damage response proteins. Finally, I will present data on how one of these new DNA damage response proteins functions to maintain genome integrity during DNA replication. Support or Funding Information NIH R01CA102729, R01GM116616, and the Breast Cancer Research Foundation