Both cell autonomous and non-autonomous processes modulate the association between replication timing and mutation rate

Oriya Vardi-Yaacov, Adar Yaacov, Shai Rosenberg, Itamar Simon

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer somatic mutations are the product of multiple mutational and repair processes, some of which are tightly associated with DNA replication. Mutation rates (MR) are known to be higher in late replication timing (RT) regions, but different processes can affect this association. Systematic analysis of the mutational landscape of 2787 tumors from 32 tumor types revealed that approximately one third of the tumor samples show weak association between replication timing and mutation rate. Further analyses revealed that those samples have unique mutational signatures and are enriched with mutations in genes involved in DNA replication, DNA repair and chromatin structure. Surprisingly, analysis of differentially expressed genes between weak and strong RT-MR association groups revealed that tumors with weak association are enriched with genes associated with cell–cell communication and the immune system, suggesting a non-autonomous response to DNA damage.

Original languageAmerican English
Article number13143
JournalScientific Reports
Volume13
Issue number1
DOIs
StatePublished - 12 Aug 2023

All Science Journal Classification (ASJC) codes

  • General

Fingerprint

Dive into the research topics of 'Both cell autonomous and non-autonomous processes modulate the association between replication timing and mutation rate'. Together they form a unique fingerprint.

Cite this