Hypermutation rate normalized by chronological time.
It is generally believed that in cells undergoing Ig somatic hypermutation, more cell divisions result in more mutations. This is because DNA synthesis and replication is thought to play roles in the known mechanisms-cytidine deamination and subsequent conversion to thymidine, uracil-DNA glycosylase-mediated repair, mismatch repair, and DNA synthesis by error-prone polymerases. In this study, we manipulated the number of cell generations by varying the rate at which cultures of a mouse cell line were replenished with fresh medium. We found that the frequency of mutants does not necessarily increase with the number of cell generations. On the contrary, a greater number of divisions can lead to a lower frequency of mutants, indicating that cell division is not a rate-limiting step in the hypermutation process. Thus, when comparing mutation rates, we suggest that rates are more appropriately expressed as mutations per day than per cell generation.
Wang
Clifford L
CL
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA. cliffw@itsa.ucsf.edu
Wabl
Matthias
M
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D001683:Biological Clocks / Q000235:genetics* / Q000276:immunology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D003470:Culture Media; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000235:genetics; D004261:DNA Replication / Q000276:immunology; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D012016:Reference Values; D027041:Somatic Hypermutation, Immunoglobulin
D003470:Culture Media; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D003564:Cytidine Deaminase