Poster Presentation 27th Lorne Cancer Conference 2015

Defining the role of cohesin in the activation of repetitive DNA in colorectal carcinogenesis                          (#316)

Huiling Xu 1 , Noreen C Eder 1 , Siddhartha Deb 1 , Danny Rangasamy 2 , Jionbae Son 1 , Mike HM Tang 1 , Dominic Paterson 1 , Robyn L Ward 3 , Nicholas J Hawkins 4 , Stephen B Fox 5 , Michael J McKay 6 , Ross D Hannan 1 , Elaine Sanij 1 , Rob G Ramsay 1
  1. Peter MacCallum Cancer Centre, East Melbounre, VIC, Australia
  2. John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
  3. Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia
  4. School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
  5. Pathology, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia
  6. University of Sydney and North Coast Cancer Institute, Lismore, NSW, Australia

Increased transcription of repetitive DNA including retrotransposable elements and ribosomal DNA (rDNA) is commonly observed in cancer cells. The molecular mechanism which activates repetitive DNA is not well understood. The cohesin complex plays a key role in mediating accurate chromosome segregation, homologous recombination and the organisation of genome structure. Our recent genome-wide analyses identify RAD21, the integral subunit of the cohesin complex, as a key transcriptional regulator of long interspersed element (LINE-1 or L1) retrotransposons. Elevated RAD21 expression tracks with re-activation of L1 expression in human colorectal cancer (CRC) cell lines and primary tumors, implicating cohesin-mediated L1 expression in inducing global genomic instability and gene dysregulation in cancer. Our study further establishes a strong association between RAD21 and rDNA transcription in CRC cell lines. RAD21 localizes in nucleoli where rDNA resides and transcribes. RAD21 deficiency resulted in altered rDNA transcription and stability. The detailed effects of rDNA transcriptional inhibition by RNA Polymerase (Pol)-I inhibitor in CRC cells in the context of elevated RAD21 expression is being investigated.