Chen, Jian-Min, Férec, Claude and Cooper, David Neil  ORCID: https://orcid.org/0000-0002-8943-8484
2015.
Complex multiple-nucleotide substitution mutations causing human inherited disease reveal novel insights into the action of translesion synthesis DNA polymerases.
Human Mutation
36
(11)
, pp. 1034-1038.
10.1002/humu.22831
|
Abstract
Translesion synthesis (TLS) DNA polymerases allow the bypass of unrepaired lesions during DNA replication. Based upon mutational signatures of a subtype of multiple-nucleotide substitution (MNS) mutations causing human inherited disease, we have recently postulated two properties of TLS DNA polymerases in DNA repair, namely, the generation of neo-microhomologies potentiating strand-misalignment, and additional microlesions within the templated inserts when recruited to stalled replication forks. To provide further support for this postulate, we analyzed the mutational signatures of a new and complex subtype of pathogenic MNS mutation. Several mutations containing long templated inserts (8–19 bp) that are highly informative with regard to their underlying mutational mechanisms, harbor imprints of TLS DNA polymerase action. Dissecting the mechanism underlying the generation of the 19-bp insert implicated repeated participation of TLS DNA polymerases in the conversion of a damaged base into a complex MNS lesion through a process of successive template switching and bypass repair.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Medicine |
| Subjects: | Q Science > QH Natural history > QH426 Genetics |
| Publisher: | Wiley-Blackwell |
| ISSN: | 1059-7794 |
| Date of Acceptance: | 23 June 2015 |
| Last Modified: | 31 Oct 2022 10:13 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/84077 |
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