# MECHANISM OF DELETION MUTAGENESIS

> **NIH NIH R01** · BRANDEIS UNIVERSITY · 1994 · $124,891

## Abstract

DESCRIPTION: Sequence analysis of deletion mutations in both E. coli and
humans has shown that deletions occur most frequently between short
repeated  sequences.  Models to explain this observation have been of two
main types:  recombinational (unequal crossing over) and replicational
(strand slippage or  misalignment).  There has been a tendency to
discount recombinational mechanisms because deletion mutations in E. coli
lack two traditional hallmarks of homologous recombination: the repeated
sequences are very often  much shorter than necessary to serve as a
substrate for RecA protein, and the  deletions occur quite readily in
RecA deletion strains, in which conventional  recombination is
eliminated.  Recent work by Dr. Lovett using a plasmid-based  system for
monitoring deletions has shown, unexpectedly, that RecA-independent
deletion formation can have unmistakable recombinational features, most
notably, deletion-associated plasmid dimerization.  On the basis of this
and  related observations, Dr. Lovett has proposed a mechanism for
deletion  formation initiated by RecA-independent pairing between nascent
strands in the  vicinity of an arrested replication fork to form a
Holiday junction, followed  by processing by other enzymes associated
with homologous recombination  reactions.  Dr. Lovett furthermore
proposes that the same mechanism may apply  to recombinational
"postreplication" repair observed on damaged DNA templates,  whose
mechanism has been obscure.

In this application, Dr. Lovett proposes to continue her study on the
mechanism of deletion formation and its relationship to recombinational
DNA  repair and sister strand exchange (plasmid dimerization) in E. coli.
The  proposed work has two broad components.  In one component, Dr.
Lovett will  analyze the effect of single DNA lesions (thymine dimers)
on the occurrence of  deletions and plasmid dimerization.Using variations
of this basic idea, she  will examine if a thymine dimer has different
effects when placed in the  leading vs. lagging strand vs. both together;
when placed in different  locations relative to the tandemly repeated
sequences that are recombining;  and when processed in strains with
mutations in various components of recombination or replication.  In the
other part of the investigation,  Dr. Lovett will define the genetics of
recA-independent deletion formation by  examining the effects of known
components of replication and recombination on  deletion formation, and
by searching for novel genes that affect the frequency  of deletion
formation.

## Key facts

- **NIH application ID:** 2190453
- **Project number:** 1R01GM051753-01
- **Recipient organization:** BRANDEIS UNIVERSITY
- **SAM.gov UEI:** MXLZGAMFEKN5
- **Principal Investigator:** SUSAN THOMAS LOVETT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $124,891
- **Award type:** 1
- **Project period:** 1994-08-01 → 1998-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2190453

## Citation

> US National Institutes of Health, RePORTER application 2190453, MECHANISM OF DELETION MUTAGENESIS (1R01GM051753-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2190453. Licensed CC0.

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