Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2014 Jul 7;206(1):29–43. doi: 10.1083/jcb.201312078

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2014 Ensminger et al.

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

PMC Copyright notice

Figure 8. — Methylated base adducts and BER intermediates interfering with replication cause distinct effects. MMS-induced N3-MeA can block replication forks (here shown for a lesion on the leading strand). Such stalled forks are mainly responsible for the strong S-phase delay after MMS. Different mechanisms exist to overcome such a blockage, with translesion synthesis being one of the predominant pathways that is not associated with SCE formation. Another process is fork regression, which leads to the formation of a chicken foot structure that can be resolved by an HR-mediated process associated with SCE formation. HR-mediated repair of single-stranded gaps, which are formed at methylated base adducts blocking lagging strand synthesis, might also contribute to SCE formation (not depicted in the model). The majority of methylated base lesions induced by MMS is repaired by BER, which is initiated by MPG. Upon interference of replication forks with SSBs induced during BER, one-ended DSBs are generated, which give rise to the formation of γH2AX foci. If unrepaired or mis-repaired, such one-ended DSBs cause chromatid breaks or translocations, respectively. Thus, one-ended DSBs arising in a BER-dependent manner are responsible for the formation of chromosomal aberrations after methylation damage. BER-induced SSBs can also lead to SCE formation.