RPA1
Animal models
Mice carrying a heterozygous missense change in one of the DNA-binding domains of Rpa1 develop lymphoid tumors, and their homozygous littermates succumb to early embryonic lethality. (#15965476#)
- Array comparative genomic hybridization of the tumors identified large-scale chromosomal changes as well as segmental gains and losses.
- The Rpa1 mutation resulted in defects in DNA double-strand break repair and precipitated chromosomal breaks as well as aneuploidy in primary heterozygous mutant mouse embryonic fibroblasts.
- The equivalent mutation in yeast is hypomorphic and semidominant and enhanced the formation of gross chromosomal rearrangements in multiple genetic backgrounds.
- Rpa1 functions in DNA metabolism are essential for the maintenance of chromosomal stability and tumor suppression.
References
Wang Y, Putnam CD, Kane MF, Zhang W, Edelmann L, Russell R, Carrion DV, Chin L, Kucherlapati R, Kolodner RD, Edelmann W. Mutation in Rpa1 results in defective DNA double-strand break repair, chromosomal instability and cancer in mice. Nat Genet. 2005 Jul;37(7):750-5. PMID: #15965476#