DNA polymerase eta is involved in hypermutation occurring during immunoglobulin class switch recombination.
J Exp Med
; 199(2): 265-70, 2004 Jan 19.
Article
in En
| MEDLINE
| ID: mdl-14734526
ABSTRACT
Base substitutions, deletions, and duplications are observed at the immunoglobulin locus in DNA sequences involved in class switch recombination (CSR). These mutations are dependent upon activation-induced cytidine deaminase (AID) and present all the characteristics of the ones observed during V gene somatic hypermutation, implying that they could be generated by the same mutational complex. It has been proposed, based on the V gene mutation pattern of patients with the cancer-prone xeroderma pigmentosum variant (XP-V) syndrome who are deficient in DNA polymerase eta (pol eta), that this enzyme could be responsible for a large part of the mutations occurring on A/T bases. Here we show, by analyzing switched memory B cells from two XP-V patients, that pol eta is also an A/T mutator during CSR, in both the switch region of tandem repeats as well as upstream of it, thus suggesting that the same error-prone translesional polymerases are involved, together with AID, in both processes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunoglobulin Class Switching
/
Somatic Hypermutation, Immunoglobulin
/
DNA-Directed DNA Polymerase
Limits:
Adult
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
J Exp Med
Year:
2004
Document type:
Article
Affiliation country:
Francia