Abstract:
:Activation-induced deaminase (AID) is essential for class switch recombination and somatic hypermutation, and it has the ability to deaminate single-stranded DNA at cytidines. Mammalian class switch regions form R-loops upon transcription in the physiological orientation. The displaced DNA strand of an R-loop is forced to wrap around the RNA-DNA hybrid; hence, it may not have complete exposure to proteins. A fundamental question concerns the extent to which AID is accessible to the displaced strand of a transcription-generated R-loop. We used a minimal R-loop to carry out high-resolution analysis of the precise locations of AID action. We found that AID deaminates on the displaced DNA strand across the entire length of the R-loop. Displaced strand locations with a WRC (where W is A or T and R is A or G) sequence are preferred targets, but there are clear exceptions. These WRC deviations may be due to steric constraints on the accessibility of AID to these sites as the displaced strand twists around the RNA-DNA duplex. This phenomenon may explain the lack of WRC site preference at the mutations surrounding class switch recombination junctions.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Yu K,Roy D,Bayramyan M,Haworth IS,Lieber MRdoi
10.1128/MCB.25.5.1730-1736.2005subject
Has Abstractpub_date
2005-03-01 00:00:00pages
1730-6issue
5eissn
0270-7306issn
1098-5549pii
25/5/1730journal_volume
25pub_type
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