L8 dna damage tolerance

What happens if mismatched base pairs are not repaired before replication

They are replicated and become mutations

What are DNA lesions

Altered or missing bases in DNA

Can all DNA lesions be repaired before replication

No

What happens when lesions are replicated by normal polymerases

They may miscode

What types of lesions block replication

CPDs and thymine glycol

What happens when replication forks stall

DNA damage response is activated

What allows replication past damaged DNA

Translesion synthesis polymerases

What is DNA damage tolerance

Ability to replicate damaged DNA

What is translesion synthesis

Replication across damaged DNA

Why can TLS polymerases bypass lesions

They have flexible active sites

What is the fidelity of TLS polymerases

Low

Do TLS polymerases have proofreading activity

No

What is the error rate of TLS polymerases

Between one in one hundred and one in ten thousand

Why is TLS useful despite errors

It allows replication to continue

How do TLS polymerases differ structurally from replicative polymerases

More open active site

What structural feature do Y family polymerases have

Little finger domain

What does the little finger domain do

Contacts DNA near lesion

How are TLS polymerases recruited

Through interaction with sliding clamp

What happens to TLS polymerase levels after damage in bacteria

They increase

What is the DNA damage response

Cellular response to DNA damage

What are the main outcomes of DNA damage response

Repair delay of cell cycle or cell death

What is the first step of DNA damage response

Recognition of damage

What happens when polymerase stalls at damage

Single stranded DNA accumulates

Why are double strand breaks dangerous

They can cause chromosomal rearrangements

What is the bacterial DNA damage response called

SOS response

How many proteins are induced in SOS response

Over forty

What proteins regulate SOS response

RecA and LexA

What is the role of RecA

Damage sensor and recombinase

What is the role of LexA

Transcriptional repressor

What happens to LexA during DNA damage

It is cleaved

What activates RecA

Binding to single stranded DNA

What happens when LexA is cleaved

SOS genes are expressed

What types of genes are induced in SOS

Repair recombination and TLS genes

What is SulA

Cell division inhibitor

What is the function of SulA

Delays cell division

What happens as DNA repair progresses

Single stranded DNA decreases

What is the role of DinI

Represses SOS response

How does DinI act

Sequesters RecA

What restores repression after repair

Newly made LexA

What detects DNA damage in eukaryotes

Sensor proteins

What protein binds single stranded DNA

RPA

What complex detects double strand breaks

MRN complex

What kinases are recruited in DNA damage response

ATR and ATM

What does ATR respond to

Single stranded DNA

What does ATM respond to

Double strand breaks

What happens when RPA accumulates

ATR is activated

What adaptor recruits ATR

ATRIP

What sliding clamp is involved in damage response

Nine one one complex

What activates ATR fully

TOPBP1

What does activated ATR do

Phosphorylates targets

What processes does ATR regulate

Cell cycle and replication

What checkpoint kinase is activated by ATR

CHK1

What is the effect of CHK1 activation

Cell cycle arrest

What happens to replication fork progression after ATR activation

It slows

What happens to origin firing after ATR activation

It is delayed

How are TLS polymerases recruited in eukaryotes

By ubiquitinated PCNA

What happens to replicative polymerases after PCNA modification

They dissociate

What does MRN stand for

Mre11 Rad50 Nbs1

What does MRN do

Binds and processes double strand breaks

What kinase is recruited by MRN

ATM

How is ATM activated

Autophosphorylation

What does activated ATM do

Phosphorylates targets

What is KU

Protein complex sensing double strand breaks

What subunits form KU

KU70 and KU80

What does KU recruit

DNA PKcs

What repair pathway is promoted by DNA PK

Non homologous end joining

What is NHEJ

Direct joining of DNA ends

Is NHEJ accurate

No

When is NHEJ mainly used

In G1 phase

What is homology directed repair

Repair using homologous template

When is homologous repair used

Late S and G2

Why is homologous repair accurate

Uses sister chromatid

What happens during NHEJ processing

Nucleotides may be removed

Why is NHEJ mutagenic

Sequence loss occurs

How do ATM and ATR control the cell cycle

By activating checkpoint kinases

What do checkpoint kinases inhibit

Cdc25 phosphatases

What happens if Cdc25 is inhibited

CDKs remain inactive

What transition is blocked by CDK2 inhibition

G1 to S

What transition is blocked by CDK1 inhibition

G2 to M

What protein halts the cell cycle after damage

P53

How is P53 activated

Phosphorylation by ATM ATR and checkpoint kinases

What form does active P53 take

Tetramer

What gene is activated by P53

P21

What does P21 do

Inhibits CDK2 cyclin E

What is the result of P21 activity

Block of G1 to S transition