Potential Implications on the Giraffe DNA Repair Pathway through the Modification of MDC1

Open Access
Wood, Brendan Rich
Area of Honors:
Bachelor of Science
Document Type:
Thesis Supervisors:
  • Douglas Cavener, Thesis Supervisor
  • Gong Chen, Honors Advisor
  • Giraffe
  • Okapi
  • MDC1
  • H2AX
  • DSB Repair
  • Double-Stranded Break
  • cancer
  • non-homologous end joining
  • homologous recombination
MDC1 is a mediator DNA-Damage Checkpoint 1 (MDC1) and is instrumental in determining the course of double-stranded break (DSB) repair pathways. Its interactions with H2AX and BRCA1 as a scaffold protein make it necessary for recruiting DNA Double Strand Break Repair proteins. Without the control and signaling from MDC1, cells will divide uncontrollably with errors resulting in tumorous growths. This indicates that MDC1 is necessary in tumor suppression. Interestingly, we have recently discovered that the giraffe and okapi have a novel splice site in exon 5 of MDC1 which results in a truncated mRNA and ultimately 250 fewer amino acids in the protein. This change in tertiary structure of MDC1 may have promoted the formation of Robertsonian translocations and led to giraffe evolving to have a karyotype of 15 chromosome pairs rather than a karyotype of 30 chromosomes as found in fellow ruminant, the cow. Giraffe and okapi modifications of the MDC1 protein could contribute to our understanding of its function in carcinogenesis and its close interactions with H2AX and BRCA1.