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Guanine- 5-carboxylcytosine base pairs mimic mismatches during DNA replication.

ABSTRACT: The genetic information encoded in genomes must be faithfully replicated and transmitted to daughter cells. The recent discovery of consecutive DNA conversions by TET family proteins of 5-methylcytosine into 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine (5caC) suggests these modified cytosines act as DNA lesions, which could threaten genome integrity. Here, we have shown that although 5caC pairs with guanine during DNA replication in vitro, G·5caC pairs stimulated DNA polymerase exonuclease activity and were recognized by the mismatch repair (MMR) proteins. Knockdown of thymine DNA glycosylase increased 5caC in genome, affected cell proliferation via MMR, indicating MMR is a novel reader for 5caC. These results suggest the epigenetic modification products of 5caC behave as DNA lesions.

SUBMITTER: Shibutani T

PROVIDER: S-EPMC4048885 | biostudies-other | 2014 Jun

REPOSITORIES: biostudies-other

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Guanine- 5-carboxylcytosine base pairs mimic mismatches during DNA replication.

Shibutani Toshihiro T Ito Shinsuke S Toda Mariko M Kanao Rie R Collins Leonard B LB Shibata Marika M Urabe Miho M Koseki Haruhiko H Masuda Yuji Y Swenberg James A JA Masutani Chikahide C Hanaoka Fumio F Iwai Shigenori S Kuraoka Isao I

Scientific reports 20140609

The genetic information encoded in genomes must be faithfully replicated and transmitted to daughter cells. The recent discovery of consecutive DNA conversions by TET family proteins of 5-methylcytosine into 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine (5caC) suggests these modified cytosines act as DNA lesions, which could threaten genome integrity. Here, we have shown that although 5caC pairs with guanine during DNA replication in vitro, G·5caC pairs stimulated DNA polymer ...[more]

PMID: 24910358

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