Mutational signature distribution varies with DNA replication timing and strand asymmetry.

Abstract:

BACKGROUND:DNA replication plays an important role in mutagenesis, yet little is known about how it interacts with other mutagenic processes. Here, we use somatic mutation signatures-each representing a mutagenic process-derived from 3056 patients spanning 19 cancer types to quantify the strand asymmetry of mutational signatures around replication origins and between early and late replicating regions. RESULTS:We observe that most of the detected mutational signatures are significantly correlated with the timing or direction of DNA replication. The properties of these associations are distinct for different signatures and shed new light on several mutagenic processes. For example, our results suggest that oxidative damage to the nucleotide pool substantially contributes to the mutational landscape of esophageal adenocarcinoma. CONCLUSIONS:Together, our results indicate an interaction between DNA replication, the associated damage repair, and most mutagenic processes.

journal_name

Genome Biol

journal_title

Genome biology

authors

Tomkova M,Tomek J,Kriaucionis S,Schuster-Böckler B

doi

10.1186/s13059-018-1509-y

subject

Has Abstract

pub_date

2018-09-10 00:00:00

pages

129

issue

1

eissn

1474-7596

issn

1474-760X

pii

10.1186/s13059-018-1509-y

journal_volume

19

pub_type

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